African American glaucoma study targets gene therapy options

Reviewed by Dr Joan O’Brien.

Investigators at the Scheie Eye Institute at the University of Pennsylvania in Philadelphia, United States, are conducting a study to gain better insight into how and why primary open-angle glaucoma (POAG) disproportionately affects the African American population. The investigators are led by Dr Joan O’Brien, director of the institute, chair of the Department of Ophthalmology and the Nina C. Mackall research professor of ophthalmology at the Perelman School of Medicine, University of Pennsylvania.

The Primary Open-Angle African American Glaucoma Genetics (POAAGG)study¹ has a population-based, cross-sectional, case-control design and focuses on investigating POAG for clues in the patients’ DNA that might help predict their risk of developing glaucoma. It is also hoped the study will reveal ways of potentially halting the disease with gene therapies before it has the chance to fully develop.

Because information from White and Asian patients may not apply to African Americans, limiting the study to this population group should provide valuable genetic insights. This is important because glaucoma is particularly devastating to African Americans, yet most of the research in glaucoma so far has involved White patients. The data show that Black people are five times more likely than White people to develop glaucoma and that their disease develops up to 10 years earlier.

Focus on community

To date, more than 10,000 patients have been recruited to participate in the study. Amassing such a high number of African American patients who were willing to donate DNA was no small feat, considering their apprehension based on their previous experiences, such as the infamous US Public Health Service Tuskegee Syphilis Study, use of DNA without individuals’ consent and potential racial targeting by police.

The investigators, many of whom are Black and have family members affected by glaucoma, reached out to community leaders to disseminate information about the study to Philadelphia residents and gain their trust. They also carried out a multimedia campaign to raise glaucoma awareness and invite people to undergo glaucoma screening.

A local radio station run by the Black community ran interviews with the investigators, to inform listeners about the importance of screening. The radio station was ultimately recognised as having informed approximately 75% of participants in the study. Screening was carried out in churches and community centres, and a van canvassed the neighbourhoods to encourage people to participate. In addition, the US National Institutes of Health provided $11 million in funding for the 5-year study to advance the cause.

When screening identified glaucoma or patients at risk for the disease, the Scheie Eye Institute provided eyecare for those patients despite the individuals’ lack of healthcare provision. The institute also provided patients with transport and lunch vouchers to overcome barriers to participation.

The study enrolment was completed in 2019. This experience led the investigators to develop a blueprint for successful recruitment strategies that they published to serve as guidelines for underserved populations.

Preliminary findings from the study

The POAAGG study involves identifying genes with mutations that might increase the risk of damage to the optic nerve. The investigators noted that this information could result in potential gene therapies that can supply an edited copy of the gene and possibly ease the medication burden for patients.

Dr Ahmara Ross, an assistant professor of ophthalmology at the Scheie Eye Institute, explained that many genes already identified as being involved in glaucoma are not the causes in African American patients – a finding that emphasises the importance of identifying the culprits in the Black community that can lead to targeted therapy.

“A lot of the genes that we know about in glaucoma don’t represent my population,” Dr Ross said. “I want to make sure that they are brought to the forefront and that, when we’re coming up with these targeted therapies, it’s targeted against their disease.”

In addition to publishing the preliminary studies of genomic sequences associated with glaucoma most often seen in African Americans, the investigators also recently identified specific genetic mutations associated with characteristics of POAG, such as intraocular pressure and nerve thickness.^2-4 As Dr O’Brien pointed out, these findings suggest that POAG might be an umbrella for a few different diseases with distinct genetic drivers.

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Joan M. O’Brien, MD

E: obrienjo@pennmedicine.upenn.edu

Dr O’Brien has no financial interest in any aspect of this report.

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References

1. Khachatryan N, Pistilli M, Maguire MG, et al. Primary Open-Angle African American Glaucoma Genetics (POAAGG) study: gender and risk of POAG in African Americans.PLoS One. 2019;14:e0218804.

2. Meer E, Qin VL, Gudiseva HV, et al. LMX1B locus associated with low-risk baseline glaucomatous features in the POAAGG study. Genes (Basel). 2021;12:1252.

3. Addis V, Chan L, Chen J, et al. Evaluation of the cirrus high-definition OCT normative database probability codes in a Black American population. Ophthalmol Glaucoma. Published online 23 May 2021.

4. Cole BS, Gudiseva HV, Pistilli M, et al. The role of genetic ancestry as a risk factor for primary open-angle glaucoma in African Americans. Invest Ophthalmol Vis Sci. 2021;62:28.