Barbara Nemesure

Prevalence and causes of visual impairment in the Barbados eye study

OBJECTIVE To determine the prevalence and causes of low vision and blindness in a predominantly black population. DESIGN Population-based prevalence study of a simple random sample of Barbados-born citizens aged 40 to 84 years. PARTICIPANTS Four thousand seven hundred nine persons (84% participation). METHODS The standardized protocol included best-corrected visual acuity (with a Ferris-Bailey chart), automated perimetry, lens gradings (LOCS II), and an interview. Participants with visual acuity of worse than 20/30, other positive findings, and a 10% sample also had an ophthalmologic examination that evaluated the cause and extent of vision loss (resulting from that cause), if any. MAIN OUTCOME MEASURES Low vision and blindness were defined as visual acuity in the better eye between 6/18 and 6/120 and visual acuity worse than 6/120, respectively (World Health Organization [WHO] criteria). RESULTS Of the 4631 participants with complete examinations, 4314 (93%) reported their race as black, 184 (4%) reported their race as mixed (black and white), and 133 (3%) reported their race as white or other. Low vision was found in 5.9% of the black, 2.7% of the mixed, and 3.0% of white or other participants. Bilateral blindness was similar for black and mixed race participants (1.7% and 1.6%, respectively) and was not found in whites. Among black and mixed participants, the prevalence of low vision increased with age (from 0.3% at 40-49 years to 26.8% at 80 years or older). The prevalence of blindness was higher (P < 0.001) for men than women at each age group (0.5% versus 0.3% at ages 40-49 and 10.9% versus 7.3% at 80 years or more). Sixty percent of blindness was due to open-angle glaucoma and age-related cataract, each accounting for more than one fourth of cases. Other major causes were optic atrophy or neuropathy and macular and other retinal diseases. Few cases of blindness were due to diabetic retinopathy (1.4%), and none were due to age-related macular degeneration. CONCLUSIONS Using the WHO criteria, prevalence of visual impairment was high in this African-origin population, particularly at older ages. Most blindness was due to open-angle glaucoma and cataract, with open-angle glaucoma causing a higher proportion of blindness than previously reported. The increased prevalence of blindness in men may be due to the increased male prevalence of glaucoma in this population and warrants further investigation. Results underline the need for blindness prevention programs, with emphasis on effective treatment of age-related cataract and enhancing strategies for early detection and treatment of open-angle glaucoma.

Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10−13). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (<1%). Further studies are needed to investigate the biological contribution of this allele to prostate cancer risk. These findings emphasize the importance of conducting genome-wide association studies in diverse populations.

Hypertension, diabetes, and longitudinal changes in intraocular pressure

PURPOSE Diabetes and hypertension are recognized risk factors for raised intraocular pressure (IOP). This report examines the longitudinal relationship of hypertension and diabetes to a 4-year IOP change in a black population with high prevalence of these conditions. DESIGN Population-based cohort study of a simple random sample of residents of Barbados, West Indies, aged >/=40 years. PARTICIPANTS A total of 2996 persons without open-angle glaucoma or receiving IOP-lowering medication at baseline. METHODS Participants underwent standardized examinations including applanation tonometry, measurement of blood pressure, and anthropometric indices; a detailed interview; various ocular measurements; and venipuncture for glycosylated hemoglobin (GHb). Diabetes was defined by self-reported physician diagnosis and hypertension by blood pressure >/=140/90 mmHg and/or treatment history. MAIN OUTCOME MEASURES The 4-year person-based IOP change between baseline and follow-up was defined as the more positive IOP difference in either eye. RESULTS An IOP >21 mmHg at baseline was more likely in black and in mixed (black and white) participants (age-gender adjusted odds ratio [OR], 3.9 and 3.8, respectively) than in whites. Similarly, these groups had more hypertension (age-gender adjusted OR, 2.4 and 2.1, respectively) and diabetes (age-gender adjusted OR, 3.9 and 1.7, respectively) than did whites. Mean IOP in black participants increased by 2.5 (standard deviation, 3.9) mmHg over 4 years. Multiple regression analyses showed that baseline diabetes history and hypertension, as well as older age, elevated GHb, higher blood pressures, and lower baseline IOP were associated with a 4-year increase of IOP. The association between diabetes history/GHb and IOP increase became borderline/nonsignificant when persons who underwent cataract surgery during follow-up were excluded. CONCLUSIONS This report provides new data on the relationship of systemic factors to longitudinal increases in IOP in an African-origin population. Results highlight the increased risk of elevated IOP in populations with high prevalences of diabetes and hypertension.

Risk factors for incident nuclear opacities

PURPOSE To evaluate risk factors for the 4-year incidence of nuclear opacities. DESIGN Population-based cohort study (85% participation at 4-year follow-up). PARTICIPANTS Two thousand six hundred nine black participants of the Barbados Eye Studies, without any nuclear opacities at baseline. METHODS Participants completed a standardized protocol at baseline and follow-up, including ophthalmic and other measurements, an interview, slit-lamp lens grading, fundus photography, and an ophthalmologic examination. Factors associated with the incidence of nuclear opacities (Lens Opacities Classification System II N > or = 2) were evaluated by logistic regression. MAIN OUTCOME MEASURE Relative risks (RR) with 95% confidence intervals (95% CI). RESULTS The 4-year incidence of nuclear opacities was 9.2% (241 of 2609) and increased greatly with age. Women were at significantly greater risk (RR = 1.8), as were persons with darker iris color (RR = 4.9), myopia (RR = 2.8), history of diabetes (RR = 1.6), leaner body mass (RR = 0.95 for each unit increase in body mass index [kg/m(2)]), and intraocular pressure (IOP)-lowering treatment (RR = 2.7), mainly with topical beta-blockers. Treated participants had a threefold RR of nuclear opacities (RR = 3.2; 95% CI, 1.6, 6.5) compared with those untreated and with IOP < or =21 mmHg. Among participants with IOP >21 mmHg, those receiving treatment (n = 33) had a fivefold RR (RR = 5.0; 95% CI, 1.7, 15.1) versus those who were untreated. The RR was similar for treated persons with and without open-angle glaucoma (RR = 3.1; 95% CI, 1.3, 7.4 and RR = 2.8; 95% CI, 0.9, 8.6 respectively) but was lower in persons with newly detected (and thus untreated) glaucoma at baseline (RR = 1.2; 95% CI, 0.6, 2.6) compared with those without open-angle glaucoma or treatment. CONCLUSIONS The 4-year risk of nuclear opacities increased with age, female gender, darker iris color, myopia, diabetes, and leaner body mass, indicating similarities with other populations. The use of topical IOP-lowering medications tripled the RR of nuclear opacities in this study, an association that requires verification from clinical trials.

Patterns of open-angle glaucoma in the Barbados Family Study

OBJECTIVE To describe the Barbados Family Study of open-angle glaucoma (OAG) and present risk factors for OAG in siblings of study probands. DESIGN Observational study of families of probands with OAG. PARTICIPANTS Two hundred thirty probands and 1056 relatives (from 207 families). METHODS Probands and their family members underwent standardized examinations, including automated perimetry, applanation tonometry, ophthalmologic evaluation, fundus photography, blood pressure, interview, and genotyping. Generalized estimation equation methods were used to evaluate risk factors. MAIN OUTCOME MEASURES Presence of OAG in the relatives, as defined by both visual field and optic disc findings, after ophthalmologic exclusion of other causes. RESULTS The median ages of probands and relatives were 68 and 47 years, respectively. In the 207 families, 29% of the probands had one relative with OAG and 10% had two or more relatives affected. Of the 1056 family members, 10% had OAG, 13% had suspect OAG, and 6% had ocular hypertension. One fifth of the 338 siblings had OAG (n = 67); they tended to be older and more often were male. Multivariate comparisons between siblings with and without OAG found that age, higher intraocular pressure (IOP), myopia, and lower diastolic blood pressure-IOP differences were related to OAG, whereas hypertension and diabetes were not. CONCLUSIONS Based on standardized protocols and examinations, approximately one quarter of the relatives had OAG or suspected OAG, despite their relatively young age. Risk factors for OAG in siblings were similar to risk factors in unrelated individuals. Analyses are ongoing to determine OAG inheritance and to localize potential gene(s) involved.

Incidence and progression of lens opacities in the Barbados Eye Studies

OBJECTIVE To provide 4-year cumulative incidence and progression rates of age-related lens opacities in a population > or =40 years of age, which is mainly of African origin. DESIGN Cohort study that reexamined surviving members of the population-based Barbados Eye Study 4 years after baseline. PARTICIPANTS Three thousand four hundred twenty-seven members of the Barbados Eye Study cohort (85% of those eligible). MAIN OUTCOME MEASURES The Lens Opacities Classification System II (LOCS II) was used at the slit lamp. Cumulative incidence was defined as the development of any nuclear, cortical or posterior subcapsular (PSC) opacities (LOCS II scores > or =2) among persons without that opacity type at baseline. Cumulative progression was defined by at least two-step increases in scores among persons with preexisting lens opacities. RESULTS The incidence of cortical opacities was about five times greater in black than white participants (age-gender adjusted relative risk = 4.7; 95% confidence interval: 1.9-11.4). In the black population, the 4-year incidence rates were 22.2% (20.4%-24.0%) for any cortical, 9.2% (8.2%-10.4%) for any nuclear, and 3.3% (2.7%-4.0%) for any PSC opacities; rates increased greatly with age. Four-year progression rates were 12.5% for cortical, 3.6% for nuclear, and 23.0% for PSC opacities, without consistent pattern by age. Women had a greater risk of cortical and nuclear opacities (P<0.05) than men and greater progression of nuclear opacities. The presence of PSC opacities at baseline seemed to at least double the incidence and progression rates of other opacities. In persons initially opacity free, single cortical opacities were the predominant type to develop at followup. Visual acuity loss frequently accompanied incident opacities. CONCLUSIONS This longitudinal study provides new population-based data on the natural history of lens opacities. Incidence and progression of opacities, especially of cortical opacities, were high. After 4 years of followup, 1 in 4 to 5 participants developed cortical opacities, 1 in 11 developed nuclear opacities, and 1 in 30 developed PSC opacities. The information obtained attests to the public health impact of age-related cataract, as well as its extent, in this and similar black populations.

Admixture and Population Stratification in African Caribbean Populations

Throughout biomedical research, there is growing interest in the use of ancestry informative markers (AIMs) to deconstruct racial categories into useful variables. Studies on recently admixed populations have shown significant population substructure due to differences in individual ancestry; however, few studies have examined Caribbean populations. Here we used a panel of 28 AIMs to examine the genetic ancestry of 298 individuals of African descent from the Caribbean islands of Jamaica, St. Thomas and Barbados. Differences in global admixture were observed, with Barbados having the highest level of West African ancestry (89.6%± 2.0) and the lowest levels of European (10.2%± 2.2) and Native American ancestry (0.2%± 2.0), while Jamaica possessed the highest levels of European (12.4%± 3.5) and Native American ancestry (3.2%± 3.1). St. Thomas, USVI had ancestry levels quite similar to African Americans in continental U.S. (86.8%± 2.2 West African, 10.6%± 2.3 European, and 2.6%± 2.1 Native American). Significant substructure was observed in the islands of Jamaica and St. Thomas but not Barbados (K=1), indicating that differences in population substructure exist across these three Caribbean islands. These differences likely stem from diverse colonial and historical experiences, and subsequent evolutionary processes. Most importantly, these differences may have significant ramifications for case‐control studies of complex disease in Caribbean populations.

Lens opacities and mortality: The Barbados Eye Studies

OBJECTIVE To evaluate the association between cataract and mortality in a black population by type of opacity, which has not been documented previously. DESIGN Population-based cohort study. PARTICIPANTS The Barbados Incidence Study of Eye Diseases reexamined the Barbados Eye Study cohort, identified through a simple random sample of predominantly black Barbadian-born citizens, aged 40 to 84 years. Of those eligible, 85% (3427 participants) had a 4-year follow-up visit. METHODS Baseline and follow-up visits included an interview, blood pressure and other measurements, and a detailed ophthalmologic examination with slit-lamp lens gradings (Lens Opacities Classification System [LOCS] II protocol). Mortality at follow-up was verified from Ministry of Health records. MAIN OUTCOME MEASURES Lens opacities were defined by a LOCS II score of 2 or more. Opacity types were classified in two ways: (1) single (cortical-only, nuclear-only, and posterior subcapsular-only) and mixed opacities; and (2) any cortical, any nuclear, or any posterior subcapsular opacities. Information on dates and causes of death was obtained from death certificates. RESULTS Cardiovascular disease was the principal cause of death in black participants (3.6%), followed by malignant neoplasms (1.4%). The cumulative 4-year mortality varied with lens types, increasing from 3.2% for those without cataract to 6.0% for cortical-only, 8.8% for nuclear-only, and 20.9% for mixed opacities. Persons with mixed opacities had a 1.6-fold increase in mortality, while controlling for other factors (age, male gender, diabetes, hypertension, obesity, cigarette smoking, cardiovascular disease, and family history of diabetes) in Cox proportional-hazards regression analyses. Persons with any nuclear opacities also had increased mortality (death rate ratio, 1.5). The death rate ratios increased with age, but peaked at age 60 to 69 years. Coexisting diabetes further increased mortality: people with mixed opacities and diabetes had a 2.7-fold increased risk of death. A trend toward increased mortality from neoplasms was observed for individuals with mixed opacities or with any nuclear opacities. CONCLUSIONS Participants with mixed opacities or any nuclear opacities had increased 4-year mortality rates, with diabetes acting as an effect modifier. This study is the first to identify a relationship between type of cataract and mortality in an African-descent population.

Evaluation of 19 susceptibility loci of breast cancer in women of African ancestry

Multiple breast cancer susceptibility loci have been identified in genome-wide association studies (GWAS) in populations of European and Asian ancestry using array chips optimized for populations of European ancestry. It is important to examine whether these loci are associated with breast cancer risk in women of African ancestry. We evaluated 25 single nucleotide polymorphisms (SNPs) at 19 loci in a pooled case-control study of breast cancer, which included 1509 cases and 1383 controls. Cases and controls were enrolled in Nigeria, Barbados and the USA; all women were of African ancestry. We found significant associations for three SNPs, which were in the same direction and of similar magnitude as those reported in previous fine-mapping studies in women of African ancestry. The allelic odds ratios were 1.24 [95% confidence interval (CI): 1.04-1.47; P = 0.018] for the rs2981578-G allele (10q26/FGFR2), 1.34 (95% CI: 1.10-1.63; P = 0.0035) for the rs9397435-G allele (6q25) and 1.12 (95% CI: 1.00-1.25; P = 0.04) for the rs3104793-C allele (16q12). Although a significant association was observed for an additional index SNP (rs3817198), it was in the opposite direction to prior GWAS studies. In conclusion, this study highlights the complexity of applying current GWAS findings across racial/ethnic groups, as none of GWAS-identified index SNPs could be replicated in women of African ancestry. Further fine-mapping studies in women of African ancestry will be needed to reveal additional and causal variants for breast cancer.

Analyses of reported family history of glaucoma: a preliminary investigation: the Barbados Eye Study Group

This study investigated the self-reported family history of open-angle glaucoma (OAG) among 4,314 black participants in the Barbados Eye Study (BES), which was based on a random sample of Barbados-born citizens between 40 and 84 years of age. Data collection included Humphrey perimetry, fundus photography, various ophthalmic and other measurements and a comprehensive interview, including family history. Results showed that participants with OAG and previous OAG treatment reported more family history; maternal history was reported twice as often as paternal history. In persons without previous OAG treatment, those with newly diagnosed OAG reported more sibling history (Odds Ratio = 4.5). The Statistical Analysis for Genetic Epidemiology (S.A.G.E.) system was used to test the transmission models for OAG in a subset of 1,048 families (5,806 individuals) with the most complete self-reported family information. The S.A.G.E. results are consistent with the existence of a major dominant allele for OAG. These results should be viewed as promising, but preliminary, since they are based on self-reported data. More definitive information is currently being collected by the Barbados Family Study of Open-angle Glaucoma.