Chronic Eye Disease Epidemiology in the Multiethnic Ophthalmology Cohorts of California Study

Summative oral presentation of the PhD dissertation to the research committee


Date
May 29, 2020 11:00

Committee Members

The committee included clinical scientists and physicians with expertise in fields related to my dissertation. I developed these projects under their guidance and mentorship, including:

Abstract

Chronic diseases of the eye are becoming more prevalent as the average age of the population continues to climb. Most non‐acute eye diseases present in adults aged 40 years or older. Epidemiologic studies over the last several decades have observed that certain eye pathologies are more common among certain racial/ethnic groups. For example, glaucoma is more prevalent in Latinos and African Americans, age‐related macular degeneration is more common in non‐Hispanic Whites, and diabetic retinopathy is more prevalent in Chinese Americans. How people are impacted by chronic eye diseases might also be related to race/ethnicity. Furthermore, degree of visual function—not just prevalence—may prove to be more informative and precise measures for characterizing disparities in eye disease.

A functional perspective of vision focuses on the experiences of individuals suffering from chronic eye diseases, and not on diagnoses of diseases made by panels of expert physicians. The impact of eye pathologies has been shown to be largely mediated through vision loss. For example, a patient with early stage glaucoma who has not suffered loss of vision—visual impairment (VI)—is likely not impaired by their disease. VI may be defined by numerous measures of vision, and all of them should be characterized to understand how chronic eye disease affects patients.

Visual acuity (VA) is a metric of central, high acuity vision that is measured using an illuminated chart the patient reads aloud to the healthcare provider. VA of 2040 or worse is a standard definition of VI that is commonly used in both the clinic and research. However, there are other, less familiar measures of VI. Visual field loss (VFL) measures the entire visual field—both central and peripheral vision—and can be used to locate specific patterns of vision loss in a patient’s visual field. However, a total score can also be used to provide a global assessment of visual ability separately for each eye. VFL is quantified on a logarithmic scale as the difference in vision from a standard population of healthy adults of the same age. One definition of VI using VFL is -2 decibels (dB) in the better‐seeing eye (BSE) of total mean deviation (MD) from an age‐adjusted standard population.

Racial/ethnic disparities in chronic eye disease should be assessed using both VFL and VA as well as other measures of vision such as contrast sensitivity. Considering continuous measures of visual function improves our understanding of the extent of vision loss for each racial/ethnic group as well as the dimensions of vision that are most affected. For example, population‐based cohort studies have demonstrated that VI defined by VFL is more common in racial/ethnic minorities compared to non‐Hispanic Whites. To see the full picture of ophthalmic illness, however, we must look beyond objective measures of visual impairment. Modern research investigates patients’ perspectives of their quality of life (QOL) to fully understand the impact of disease and to design effective treatments.

Health‐related quality of life (HRQOL) is a latent construct with numerous definitions, but overall is used to measure the value of life for several domains including the ability to perform tasks and socioemotional well‐being. HRQOL has been shown to vary among racial/ethnic groups for cancer patients after adjusting for demographic factors and socioeconomic status (SES). Cultural differences in beliefs of how health is related to illness and death have been identified as explanations for racial/ethnic differences in HRQOL among terminal patients. Race/ethnicity is related to how people find meaning during the end of life. Might similar differences exist in how people find value related to their vision when suffering from chronic eye disease?

Vision‐specific QOL (VSQOL) has been employed by ophthalmologists and investigators for several decades to capture the value of life related to one’s visual ability. VSQOL is another quantitative measure of visual function—like VA and VFL—but focuses on patients’ subjective experiences. Because chronic eye diseases are predominantly disabling only when they cause VI, the association of VI and VSQOL is essential to understanding how chronic eye disease affects patients. VSQOL has been used as an outcome variable in clinical trials to assess whether ophthalmologic interventions are effective in treating chronic eye diseases. In addition, VSQOL has also been used at the population level to assess the perception of vision loss and how it impacts daily life in the community. This information is useful for prioritizing public health resources to improve domains of visual health that are most meaningful for multiethnic groups. Of course, this is only relevant if race/ethnicity modifies the relationship between visual impairment and VSQOL.

Although VSQOL is a subset of QOL, differences have been identified in the literature. Only VSQOL, but not HRQOL, appears to be affected by vision loss. VSQOL is specific to vision but not to health in general, which may explain why broader measures of QOL are not sensitive to VI. Furthermore, VSQOL is measured using instruments that were developed and validated for multiethnic populations. Given that VSQOL is a more specific domain than HRQOL and has demonstrated construct validity in diverse populations, do cultural beliefs and other racial/ethnic factors modify the association between patients’ subjective experiences and quantitative measures of visual impairment? Variation in the prevalence of chronic eye diseases exist by race/ethnicity. Do people experiencing the same quantitative loss in vision have similar magnitudes and patterns of reduced QOL specific to their vision, regardless of their race/ethnicity?

VSQOL has been associated with VA, VFL, and other continuous measures of visual impairment among non‐Hispanic Whites, Latinos, and populations of African descent outside the US. But no studies have assessed these associations in large groups of African Americans or cross‐cultural studies of the most populous racial/ethnic groups in the United States (US). The primary aim of the first two papers in this dissertation are to elucidate how VSQOL may be differentially impacted by VFL for major US racial/ethnic groups. In the first paper we validate modern psychometric measures of VSQOL in the largest, population‐based cohort of chronic eye disease ever conducted in African Americans. In this study, we assess whether clinically meaningful differences in VSQOL are associated with similar magnitudes and patterns of VFL in non‐Hispanic White and Latino populations. The second paper is a pooled analysis concerned with harmonizing methods to assess whether similar associations between VFL and VSQOL exist for Latinos, Chinese Americans, and African Americans. The second study concludes our assessment of whether differences exist in how vision loss impacts VSQOL by race/ethnicity. From here we move on to investigate why differences in chronic eye diseases exist in the first place, and whether air pollution might be an important explanatory exposure.

Recall that Latinos and African Americans have a higher prevalence of open angle glaucoma (OAG), which is the leading cause of irreversible blindness globally. However, the scientific community has not identified why this disparity exists. Several genetic studies have found evidence that a limited number of genetic markers may increase the risk of OAG among participants with African Ancestry. But small effects do not fully explain the relatively large racial/ethnic difference.

In the third paper of this dissertation we identify a modest association between traffic‐related air pollution (TRAP) and reduced blood flow to retinal vessels implicated in OAG in a cohort of African Americans. The pathophysiology of OAG involves the death of retinal ganglion fiber cells, possibly due to deleterious effects of the retinal microvasculature surrounding the optic nerve head (ONH). TRAP has been shown to cause damage to microvasculature in other areas of the body, leading to cardiovascular disease, stroke, vascular Alzheimer’s disease and overall mortality. Also, exposure to TRAP has been shown to be greater for impoverished people and people of color in the US. Optical coherence tomography angiography (OCTA) is a noninvasive imaging methodology that was used to measure retinal blood flow in the vessels surrounding the ONH. These findings complement recent studies of large hospital biobanks that identified TRAP measured at patient addresses was associated with changes in the thickness of retinal nervous tissue associated. We propose that the next population‐based study of eye disease should implement OCTA to more precisely assess TRAP exposure and retinal blood flow in a larger cohort of participants.

This dissertation characterizes multiethnic disparities in domains of chronic eye disease epidemiology including subjective experience related to vision, objective visual function, anatomical measurements of the eye and environmental exposures. Study participants are from the Multiethnic Ophthalmology Cohorts of California Study (MOCCaS), which is composed of population‐based cohorts of Latino, Chinese American, and African American participants living in Los Angeles County. Technical abstracts are available later in this dissertation at the beginning of each chapter. The first paper proposes and assesses the psychometric validity of a VSQOL instrument in a large cohort of African Americans for the first time. Associations are identified between patterns of VFL and VSQOL related to tasks and socioemotional well-being. The second paper identifies racial/ethnic differences in VFL and VSQOL across all three racial/ethnic groups using harmonized methods. The final paper investigates a burgeoning hypothesis that TRAP is associated with OAG as measured by blood perfusion to vessels in the eye.

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Dom Grisafe
MD Candidate | PhD Epidemiology

Epidemiologist studying chronic disease in population-based cohort studies

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