IMPORTANCE\nMultiple studies have found an increased prevalence, younger age at onset, and more severe course of glaucoma in people of African descent, but these findings are based on studies conducted outside Africa.\n\n\nOBJECTIVE\nTo determine the prevalence of glaucoma in an urban West African population of adults.\n\n\nDESIGN AND SETTING\nA population-based, cross-sectional study of adults 40 years and older conducted from September 1, 2006, through December 31, 2008, from 5 communities in Tema, Ghana.\n\n\nPARTICIPANTS\nParticipants from randomly selected clusters underwent a screening examination that consisted of visual acuity, frequency doubling perimetry, applanation tonometry, and optic disc photography. Participants who failed any of these tests were referred for complete examination, including gonioscopy, standard automated perimetry, and stereoscopic optic disc photography.\n\n\nRESULTS\nA total of 6806 eligible participants were identified, and 5603 (82.3%) were enrolled in the study. The field examination referred 1869 participants (33.3%) to the clinic examination, and 1538 (82.2%) came for complete examination. A total of 362 participants were identified as having glaucoma of any type and category. Primary open-angle glaucoma was the underlying diagnosis in 342 participants (94.5%). The prevalence of primary open-angle glaucoma was 6.8% overall, increasing from 3.7% among those 40 to 49 years old to 14.6% among those 80 years and older, and was higher in men than in women in all age groups, with an overall male-female prevalence ratio of 1.5. Of the participants with glaucoma, 9 (2.5%) were blind using World Health Organization criteria, and only 12 (3.3%) were aware that they had glaucoma.\n\n\nCONCLUSIONS AND RELEVANCE\nThe prevalence of glaucoma is higher in this urban West African population than in previous studies of people of East or South African and of non-African descent. Strategies to identify affected persons and effectively manage the burden of glaucoma are needed in West Africa.

Prevalence of Glaucoma in an Urban West African Population: The Tema Eye Survey

Major review: Molecular genetics of primary open-angle glaucoma.

Characterizing the "POAGome": A bioinformatics-driven approach to primary open-angle glaucoma.

https://stacks.cdc.gov/view/cdc/40489/cdc_40489_DS1.pdf

The Philadelphia Glaucoma Detection and Treatment Project: Detection Rates and Initial Management

Purpose To estimate the population frequencies of all common mitochondrial variants and ancestral haplogroups among 1,999 subjects recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) Study, including 1,217 primary open-angle glaucoma (POAG) cases and 782 controls, and to identify ancestral subpopulations and mitochondrial mutations as potential risk factors for POAG susceptibility. Methods Subject classification by characteristic glaucomatous optic nerve findings and corresponding visual field defects, as defined by enrolling glaucoma specialists, stereo disc photography, phlebotomy, extraction of total DNA from peripheral blood or saliva, DNA quantification and normalization, PCR amplification of whole mitochondrial genomes, Ion Torrent deep semiconductor DNA sequencing on DNA pools ("Pool-seq"), Sanger sequencing of 3,479 individual mitochondrial DNAs, and bioinformatic analysis. Results The distribution of common African haplogroups within the POAAGG study population was broadly similar to prior surveys of African Americans. However, the POAG case population was found to be enriched in L1c2 haplogroups, which are defined in part by missense mutations m.6150G>A (Val83Ile, odds ratio [OR] 1.8, p=0.01), m.6253C>T (Met117Thr, rs200165736, OR 1.6, p=0.04), and m.6480G>A (Val193Ile, rs199476128, OR 4.6, p=0.04) in the cytochrome c oxidase subunit 1 (MT-CO1) gene and by a variant, m.2220A>G (OR 2.0, p=0.01), in MT-RNR2, which encodes the mitochondrial ribosomal 16s RNA gene. L2 haplogroups were predicted to be overrepresented in the POAG case population by Pool-seq, and the difference was confirmed to be significant with Sanger sequencing, that targeted the L2-associated variants m.2416T>C (rs28358580, OR 1.2, p=0.02) and m.2332C>T (OR 1.2, p=.02) in MT-RNR2. Another variant within MT-RNR2, m.3010G>A (rs3928306), previously implicated in sensitivity to the optic neuropathy-associated antibiotic linezolid, and arising on D4 and J1 lineages, associated with Leber hereditary optic neuropathy (LHON) severity, was confirmed to be common (>5%) but was not significantly enriched in the POAG cases. Two variants linked to the composition of the gut microbiome, m.15784T>C (rs527236194, haplogroup L2a1) and m.16390G>A (rs41378955, L2 haplogroups), were also enriched in the case DNA pools. Conclusions These results implicate African mtDNA haplogroups L1c2, L1c2b, and L2 as risk factors for POAG. Approximately one in four African Americans have these mitochondrial ancestries, which may contribute to their elevated glaucoma risk. These haplogroups are defined in part by ancestral variants in the MT-RNR2 and/or MT-CO1 genes, several of which have prior disease associations, such as MT-CO1 missense variants that have been implicated in prostate cancer.

Michael Chua

Papers

The Primary Open-Angle African American Glaucoma Genetics Study: Baseline Demographics