Seeing in Color: Inclusion and Characterization of Hereditary Eye Disease in African Americans

Abstract

Purpose: Hereditary eye diseases (HEDs) are individually rare but affect millions globally. The era of molecular genetics has ushered major advances in the study of these disorders; however, the inclusivity and population diversity of this research is unknown. Questions on the accuracy and applicability of these findings in diverse populations, especially African American patients, came up consistently during counselling sessions. This also raised the possibility of missed opportunities for broader understanding of these rare diseases. We conducted a literature review to measure the representation of African Americans in genomic research surrounding nine HEDs.

Methods: A detailed literature search using a predetermined set of search terms for each of nine HED categories was performed across PubMed, Embase, Web of Science, and Scopus focusing on studies published between Jan 1990 and July 2021. Predetermined inclusion criteria were applied to filter the sources.

Results: We identified 46 studies clearly reporting HED characterization in African Americans. Analysis of these inclusive studies revealed unique findings demonstrating the known usefulness of including diverse cohorts in genomics research.

Conclusions: HED characterization in diverse participants, specifically African Americans, is identified as a knowledge gap area. Genomic research is more applicable to patients when conducted in populations that share their ancestral background. Greater inclusion of African Americans in ophthalmic genetics research is a scientific imperative and a needed step in the pursuit of the best possible patient care for populations of all ancestries.

Translational Relevance: This work reveals gaps in genomic research in African Americans with HEDs.

Introduction

African Americans make up approximately 12% of the American population.¹ However, genomic research in patients of African ancestry lags behind that in other populations of European or Asian descent. The 2018 NHGRI-EBI GWAS catalog only included 2.4% of individuals of African ancestry.² Although race is a social construct and not a biological category, it can be a proxy for identifying shared ancestral backgrounds of individuals. It is well-understood that patients benefit most from genomic research conducted in populations that share their ancestral background.³ We performed a thorough search of the literature looking to identify work specifically reporting on the genotype, phenotype, and management of hereditary eye disease (HED) in the African American population. We specifically researched the following nine HEDs owing to their high prevalence and incidence: retinitis pigmentosa, Stargardt disease, corneal dystrophy, optic atrophy, congenital glaucoma, congenital cataracts, aniridia, oculocutaneous albinism, and retinoblastoma. We also selected these diseases to reflect the breadth of HEDs investigated by the field of ophthalmic genetics, with diseases affecting various ocular structures in different segments of the eye. 

Of note, we defined African Americans as individuals who are a part of the diaspora of Black groups from Africa in the United States. As such, any publications studying populations of African origin residing in Africa or outside the United States were excluded. 

Methods

A two-pronged approach was used with an initial search of the PubMed database of the National Library of Medicine followed by a review of the Embase, Web of Science, and Scopus databases to be as comprehensive as possible. Using the advanced search feature, we searched for mention of keywords (Table 1) related to the specific ocular dystrophies investigated in our study. These included names of syndromes, abbreviations, and known associated genes. With each of these keywords, we searched for the mention of “African-American” and “African American” in the title or abstract field to narrow our search to papers that specifically focused on our target research demographic. “African” was later used as a secondary check for literature focused on those of African ancestry in the United States. Use of the term “Black” to target our population of interest was found to be an ineffective search criterion as it was not specific to the racial or ethnic categorization and was often used as a qualitative descriptor of images or figures. 

Table 1.

 

Search Criteria Used for PubMed Search to Identify Relevant Works

 

All gathered sources were filtered through previously determined exclusion criteria listed here. Single patient or single family reports were excluded unless insight into the genetic basis of the associated disease was clear from the title or abstract. Sources were excluded if they were not specific to the diseases of interest or if they did not report findings specific to our target population in their results, discussion, figures, or tables. We also excluded studies from before 1990 to focus on the era of molecular medicine. Our review was finalized on July 1, 2021, so publications after this date were not included. Finally, we excluded all journal articles and relevant abstracts not published in peer-reviewed sources. 

Results

We found 14 oculocutaneous albinism,^4–18 9 retinitis pigmentosa,^19–27 8 corneal dystrophy,^28–35 6 optic atrophy,^36–40 4 retinoblastoma,^41–44 3 Stargardt disease,^45–47 and 2 congenital glaucoma^48,49 studies with specific characterization of disease in African American patients (Fig. 1). For two of our HEDs, congenital cataracts and aniridia, there were no studies found that characterized disease in African American patients based on our search criteria. 

Figure 1.

 

(A) Total number of 1990–2021 PubMed publications mentioning target disease in title/abstract as of July 27, 2021. (B) Number of HED studies with African American population-specific characterization of disease. (C) Comparison of the total number of HED studies published on PubMed with mention of target disease in title/abstract published vs. studies characterizing HED in African American patients between 1990 and July 2021. CC, congenital cataract; OCA, oculocutaneous albinism; PCG, primary congenital glaucoma.

Further analysis of studies that were inclusive of African American patients demonstrated the known usefulness of diverse genomics research by reporting novel disease-associated variants, challenging classifications of benign and pathogenic variants, proposing previously unreported genotype–phenotype correlations, and expanding documented manifestations of these diseases in more diverse populations (Fig. 2). Table 2 further highlights some of these findings. 

Figure 2.

 

Unique molecular findings from studies inclusive of disease characterization in African American patients that inform understanding and diagnosis of disease. OCA, oculocutaneous albinism; PCG, primary congenital glaucoma.

Table 2.

 

Sample of a Few Notable Findings from HED Studies With African American Cohorts

 

Discussion and Future Directions

Patients benefit most from genetic research conducted in populations that share their ancestral background.³ Yet, few studies document the presentations and characterization of HEDs in African American patients. We show that studies investigating diverse populations report unique and interesting findings (Table 2). Of note, we see results with diagnostic implications including the identification of potentially pathogenic molecular markers,^{4,6–8,20,26,32,34,35,45} reclassification of proposed pathogenic markers as benign,^20,48 and greater phenotypic variation to be added to illness scripts of disease.^20,24 With regard to treatment, identification of disease-causing genetic variants has therapeutic implications as genome modifying tools are being developed to treat these conditions. Additionally, we see that race is correlated with differential treatments and outcomes of treatment being offered to patients highlighting a health disparity that can be addressed by clinicians.^33,42 

These findings should not be interpreted to mean that these HEDs present in unique and different ways in African American patients, because we know that race alone is not a corollary of genetic divergence. However, by including patients of different races and ethnicities, we increase the pool of genomic data. This finding emphasizes the need for genomics research to be conducted in intentionally heterogeneous populations. By diversifying the ancestries of the populations included in our ophthalmic genetics studies, we allow for increased accuracy, novel discoveries, and better diagnostic and prognostic tools, and pave the path for more equitable generalizability of findings and access to treatments. Although race is not a biological category, diversity in ancestry provides a richer scientific sample from which conclusions of greater power and accuracy can be drawn and treatments with wider usefulness can be developed. 

Some limitations of this work include the possibility that some studies were missed in our search owing to methodological limitations including term selection and exclusion criteria. It is also possible that additional work conducted by contributors in the field did not include information on the demographic criterion central to this study in the title or abstract, namely, African American race. Despite these possible limitations, this work demonstrates a lack of inclusion of African American patients when sampling a large body of ophthalmic genetics literature. 

With this knowledge gap identified, we are left with the question of what can be done and turn our attention to future directions. Much work has already been done to bring needed attention to disparities in vision health and informing strategies for steps forward.^50–52 Other recent efforts have focused on providing guidance on the use and reporting of race and ethnicity in health research and medical journals.^53,54 Practical steps to increase inclusion and diversity specifically in genetics research have been identified by researchers outside of the field of ophthalmology, including Bentley et al. in 2017.³ We adapted some of these steps in Table 3 to be specifically pertinent to the field of ophthalmic genetics. These recommendations provide a path forward for individual researchers and the field of ophthalmic genetics as a whole as we continue to build a more equitable research future. 

Table 3.

 

Challenges and Recommendations for Increasing Diversity in Research, Derived From Bentley, 2017³

 

Conclusions

Genomic research conducted in populations of shared ancestral background is more likely to be applicable to patients in that population.³ HED characterization in diverse participants, specifically African Americans, is identified as a knowledge gap area; addressing this gap will lead to a better understanding of HEDs in broader populations. Greater inclusion of African Americans in ophthalmic genetics research is a scientific imperative and is a needed step in the pursuit of the best possible patient care. 

Acknowledgments

The authors are grateful to the DIVRO Program for their support of this research. This work was supported by the Intramural Research Program of the National Eye Institute, part of the National Institutes of Health (NIH). 

Funding provided by the NEI Intramural Research Fund and Diversity In Vision Research and Ophthalmology (DIVRO) Program, NIH. 

Disclosure: A.C. Owete, None; R. Ionin, None; L.A. Huryn, None; C.A. Cukras, None; D. Blain, None; A.R. Agather, None; R.B. Hufnagel, None; B.P. Brooks, None; K. Nwanyanwu, None; W.M. Zein, None