Eyes of Africa: The Genetics of Blindness: Study Design and Methodology.

BACKGROUND: This report describes the design and methodology of the "Eyes of Africa: The Genetics of Blindness," a collaborative study funded through the Human Heredity and Health in Africa (H3Africa) program of the National Institute of Health. METHODS: This is a case control study that is collecting a large well phenotyped data set among glaucoma patients and controls for a genome wide association study. (GWAS). Multiplex families segregating Mendelian forms of early-onset glaucoma will also be collected for exome sequencing. DISCUSSION: A total of 4500 cases/controls have been recruited into the study at the end of the 3rd funded year of the study. All these participants have been appropriately phenotyped and blood samples have been received from these participants. Recent GWAS of POAG in African individuals demonstrated genome-wide significant association with the APBB2 locus which is an association that is unique to individuals of African ancestry. This study will add to the existing knowledge and understanding of POAG in the African population.

Glaucoma care and follow-up in sub-Saharan Africa: Is there a need for modification of counselling practices to improve awareness, knowledge and treatment acceptance profiles? A prospective cross-sectional study.

BACKGROUND: Blindness from glaucoma is prevalent in parts of Africa. Lack of awareness, late diagnosis, poor acceptance and compliance to treatment as well as unorthodox care practices are among many contributing factors. Strategies that improve glaucoma awareness and treatment acceptance are required to resolve this trend. PURPOSE: To evaluate the influence of counselling on glaucoma awareness, willingness to accept glaucoma surgery and eye care practices among primary open-angle glaucoma patients on medical treatment. METHODS: A prospective cross-sectional interviewer-administered questionnaire-based study evaluating the demographics, glaucoma awareness, acceptance of operative care and use of traditional eye medications among patients with primary open-angle glaucoma on medical treatment followed up over a 12-month period. RESULTS: A total of 120 eligible participants were recruited. Glaucoma awareness and basic knowledge were 93.3 and 12%, respectively. Educational attainment and positive family history were associated with glaucoma awareness (p = 0.027 and p = 0.042, respectively). Seventy-five (62.5%) participants accepted glaucoma surgery as a treatment option. However, the duration of medical treatment was inversely related to the acceptance of glaucoma surgery (odds ratio = - 0.390, p = 0.009). Twelve (10.5%) participants use traditional eye medication for their current eye problem. CONCLUSION: Glaucoma counselling should be performed with a content template that delivers all relevant information to patients and caregivers. This will bridge gaps in knowledge and improve the early presentation, acceptance of glaucoma surgery and eye care practices.

Association of Genetic Variants With Primary Open-Angle Glaucoma Among Individuals With African Ancestry.

Importance: Primary open-angle glaucoma presents with increased prevalence and a higher degree of clinical severity in populations of African ancestry compared with European or Asian ancestry. Despite this, individuals of African ancestry remain understudied in genomic research for blinding disorders. Objectives: To perform a genome-wide association study (GWAS) of African ancestry populations and evaluate potential mechanisms of pathogenesis for loci associated with primary open-angle glaucoma. Design, Settings, and Participants: A 2-stage GWAS with a discovery data set of 2320 individuals with primary open-angle glaucoma and 2121 control individuals without primary open-angle glaucoma. The validation stage included an additional 6937 affected individuals and 14 917 unaffected individuals using multicenter clinic- and population-based participant recruitment approaches. Study participants were recruited from Ghana, Nigeria, South Africa, the United States, Tanzania, Britain, Cameroon, Saudi Arabia, Brazil, the Democratic Republic of the Congo, Morocco, Peru, and Mali from 2003 to 2018. Individuals with primary open-angle glaucoma had open iridocorneal angles and displayed glaucomatous optic neuropathy with visual field defects. Elevated intraocular pressure was not included in the case definition. Control individuals had no elevated intraocular pressure and no signs of glaucoma. Exposures: Genetic variants associated with primary open-angle glaucoma. Main Outcomes and Measures: Presence of primary open-angle glaucoma. Genome-wide significance was defined as P < 5 × 10-8 in the discovery stage and in the meta-analysis of combined discovery and validation data. Results: A total of 2320 individuals with primary open-angle glaucoma (mean [interquartile range] age, 64.6 [56-74] years; 1055 [45.5%] women) and 2121 individuals without primary open-angle glaucoma (mean [interquartile range] age, 63.4 [55-71] years; 1025 [48.3%] women) were included in the discovery GWAS. The GWAS discovery meta-analysis demonstrated association of variants at amyloid-ß A4 precursor protein-binding family B member 2 (APBB2; chromosome 4, rs59892895T>C) with primary open-angle glaucoma (odds ratio [OR], 1.32 [95% CI, 1.20-1.46]; P = 2 × 10-8). The association was validated in an analysis of an additional 6937 affected individuals and 14 917 unaffected individuals (OR, 1.15 [95% CI, 1.09-1.21]; P < .001). Each copy of the rs59892895*C risk allele was associated with increased risk of primary open-angle glaucoma when all data were included in a meta-analysis (OR, 1.19 [95% CI, 1.14-1.25]; P = 4 × 10-13). The rs59892895*C risk allele was present at appreciable frequency only in African ancestry populations. In contrast, the rs59892895*C risk allele had a frequency of less than 0.1% in individuals of European or Asian ancestry. Conclusions and Relevance: In this genome-wide association study, variants at the APBB2 locus demonstrated differential association with primary open-angle glaucoma by ancestry. If validated in additional populations this finding may have implications for risk assessment and therapeutic strategies.

Mapping the pathways to eye care in a rural south-east Nigerian population: any implications for practice, eye care programs and policy?

INTRODUCTION: The appropriateness of the initial pathway to care, especially eye care, is critical for timeliness and outcomes of care. Individual-dependent and health system-determined factors influence the preferred initial pathway to care. This study aimed to map the initial pathways to eye care in a rural population in south-east Nigeria and identify the associated factors. METHODS: This study was a population-based, cross-sectional descriptive survey conducted in Abagana, a rural south-east Nigeria community, in September 2011. Using a researcher-administered questionnaire, data on participants' sociodemographics, preferred initial eyecare pathway when confronted with an eye disorder and their reason(s) for the choice of pathway were collected. Descriptive and analytical statistics were performed. Regression analysis was used to identify independent predictors of visiting an ophthalmologist when confronted with an eye disorder. In all comparisons, p < 0.05 was considered statistically significant. RESULTS: The participants (n = 501: 263 men; 238 women) were aged 48.9±16.3 years (range 18-93 years). The majority of the participants were married (339; 67.7%) and possessed formal education (415; 82.8%). The participants' frequently preferred initial pathways to eye care were to consult a patent medicine dealer (178; 35.0%), to consult an ophthalmologist (165; 33.0%), and to self-medicate (125; 25.0%). Possession of formal education (odds ratio 0.3; 95% confidence interval 0.1-0.5; p < 0.001) was the only significant sociodemographic predictor of consulting an ophthalmologist when confronted with an eye disorder The participants' main reasons for not consulting an ophthalmologist were ignorance (190; 56.5%), cost (199; 59.2%), and restricted spatial access (228; 67.9%). CONCLUSIONS: The majority of the respondents chose an inappropriate eyecare pathway in the event of an eye disorder. The reported barriers to appropriate pathway selection are amenable to community-based eye health education, enhanced affordability, and even distribution of eyecare services. Integrating other alternative care pathways into orthodox eye care should be considered.

Ten-year rural experience of surgical eye removal in a primary care center south-eastern Nigeria.

INTRODUCTION: Surgical removal of the eye usually reflects the pattern of severe ocular diseases and the level of development and socio-cultural dynamics in each specific setting. In Nigeria there have been several reports of causes of surgical eye removal in urban tertiary eye-care centers. This study determined the pattern of surgical eye removal in a rural primary eye-care facility (hospital) in South-eastern Nigeria. METHODS: A retrospective chart review was performed for all patients who had surgical removal of the eye between January 2002 and January 2012 at the eye unit of the Presbyterian Joint Hospital, Ohaozara, Ebonyi State, South-eastern Nigeria. Data collected included age, sex, diagnosis and the eye affected. The diagnosis was further categorized into degenerative lesions, infections, trauma and neoplasm. The statistical package for social sciences was used for data analysis. RESULTS: Two hundred and twenty-six eyes from 226 patients were surgically removed within the study period from 52.2% (n = 118) males and 47.8% (n = 108) females (ratio: 1.1:1; p = 0.5). The mean age of the cohort was 47.6 ± 20.2 years (range 2-82). Children aged 0-10 years were 8.4% while those over 60 years comprised 23.4% of the study population. The three most common causes of surgical removal of the eye were severe eye infections 60.6% (n = 137), degenerative eye diseases (staphyloma) 13.3% (n= 30) and severe eye injury 11.5% (n = 26). Retinoblastoma 6.2% (n = 14) was the commonest tumour type seen. CONCLUSION: The most common cause of surgical eye removal was severe ocular infections followed by degenerative eye diseases. More males than females had their eyes surgically removed. Over half of those who had their eyes removed were aged 51 to over 60 years. The commonest cause of eye removal among children was retinoblastoma. These causes are largely preventable and avoidable. With intensive eye health education and the provision of adequate eye-care facilities this trend can be reversed.

Determinants of participation in glaucoma genomic research in South East Nigeria: A cross-sectional analytical study.

BACKGROUND: Genomic research advances the understanding of human health and disease. It also drives both the discovery of salient genetic association(s) as well as targeted screening, diagnostic and therapeutic strategies. Human subject participation is crucial for the success of genomic research. METHODS: This is a cross sectional analytical study conducted at two tertiary centers in Enugu Southeast Nigeria. Semi structured questionnaires were administered to eligible consenting participants. Data on their demographics, willingness to participate in genomic research and motivation for participation were obtained. Data was analyzed using Stata version 17 and summarized using median, frequencies and interquartile range(IQR). Associations between covariates were evaluated with Chi square test and multivariable logistic regression. RESULTS: Among 228 glaucoma subjects who participated in our study,119(52.2%) were female and 109(47.8%) were male. The median age was 64 years(IQR = 50-76). Although 219 (96.0%) participants expressed willingness to participate in a glaucoma genetic study, only 27(11.9%) of them will be willing to participate if there will not be feedback of results to participants (χ2 = 18.59, P<0.001). No participant expressed willingness to submit ocular tissue samples. Majority (96.2%) of subjects will not participate if the intended research required submission of body samples after death. Desire to know more about glaucoma (63%) was the most common reason for participation. In a multivariable logistic model, subjects between 61-90 years (p = 0.004, OR = 7.2) were 7 times more likely to express willingness to participate in glaucoma genetic research after adjusting for other covariates when compared to subjects aged 41-60 years. Other covariates did not influence participants' willingness. CONCLUSION: Glaucoma subjects are more likely to be willing to participate in genetic research, if they would receive feedback of results. Willingness to participate in genetic research is significantly associated with age. LIMITATIONS: We did not evaluate the salient options for feedback of results to participants in our study.

Comparing posture induced intraocular pressure variations in normal subjects and glaucoma patients.

AIM: To compare the posture-induced variations in intraocular pressure (IOP) between the primary open angle glaucoma (POAG) and non-glaucomatous eyes. METHODS: A case-controlled age matched study was conducted in 55 successive newly diagnosed POAG and 56 non-glaucomatous patients seen in glaucoma clinic and general outpatient eye clinic in the Alex Ekwueme University Teaching Hospital, Abakaliki. The IOPs of eligible correspondents were measured with Perkin's hand-held tonometer in the sitting, supine flat and supine with pillow positions respectively. Measurement of IOP in each position was done after 15min of assuming such posture. RESULTS: The IOP difference between the sitting and supine flat position was significantly higher in the POAG than non-glaucoma subjects (7.68±2.08 vs 4.03±0.13 mm Hg, P<0.001). The IOP difference between the sitting and supine with pillow positions was 2.61±1.49 mm Hg for POAG and 1.44±0.70 mm Hg in non-glaucoma (P<0.001), while difference between supine flat and supine with pillow positions was 5.07±2.24 mm Hg in POAG and 2.59±0.66 mm Hg in non-glaucomatous patients (P<0.001). CONCLUSION: Greater variations in posture induced IOP occurred in POAG patients than non-glaucomatous. The posture induced IOP variation is lowest in the sitting position and highest in the supine flat position. Evaluation of posture induced IOP changes may be an important tool in the management of glaucoma.

Traditional eye medicine use by newly presenting ophthalmic patients to a teaching hospital in south-eastern Nigeria: socio-demographic and clinical correlates.

BACKGROUND: This study set out to determine the incidence, socio-demographic, and clinical correlates of Traditional Eye Medicine (TEM) use in a population of newly presenting ophthalmic outpatients attending a tertiary eye care centre in south-eastern Nigeria. METHODS: In a comparative cross-sectional survey at the eye clinic of the University of Nigeria Teaching Hospital (UNTH), Enugu, between August 2004 - July 2006, all newly presenting ophthalmic outpatients were recruited. Participants' socio-demographic and clinical data and profile of TEM use were obtained from history and examination of each participant and entered into a pretested questionnaire and proforma. Participants were subsequently categorized into TEM- users and non-users; intra-group analysis yielded proportions, frequencies, and percentages while chi-square test was used for inter-group comparisons at P = 0.01, df = 1. RESULTS: Of the 2,542 (males, 48.1%; females, 51.9%) participants, 149 (5.9%) (males, 45%; females, 55%) used TEM for their current eye disease. The TEMs used were chemical substances (57.7%), plant products (37.7%), and animal products (4.7%). They were more often prescribed by non-traditional (66.4%) than traditional (36.9%) medicine practitioners. TEMs were used on account of vision loss (58.5%), ocular itching (25.4%) and eye discharge (3.8%). Reported efficacy from previous users (67.1%) and belief in potency (28.2%) were the main reasons for using TEM. Civil servants (20.1%), farmers (17.7%), and traders (14.1%) were the leading users of TEM. TEM use was significantly associated with younger age (p < 0.01), being married (p < 0.01), rural residence (p < 0.01), ocular anterior segment disease (p < 0.01), delayed presentation (p < 0.01), low presenting visual acuity (p < 0.01), and co-morbid chronic medical disease (p < 0.01), but not with gender (p = 0.157), and educational status (p = 0.115). CONCLUSION: The incidence of TEM use among new ophthalmic outpatients at UNTH is low. The reasons for TEM use are amenable to positive change through enhanced delivery of promotive, preventive, and curative public eye care services. This has implications for eye care planners and implementers. To reverse the trend, we suggest strengthening of eye care programmes, even distribution of eye care resources, active collaboration with orthodox eye care providers and traditional medical practitioners, and intensification of research efforts into the pharmacology of TEMs.

Prevalence of Human Immunodeficiency Virus Seropositivity among Eye Surgical Patients at a Rural Eye Care Facility in South-Eastern Nigeria.

PURPOSE: To determine the prevalence of human immunodeficiency infection among patients who underwent surgery at a rural eye care facility in southeastern Nigeria. MATERIALS AND METHODS: A retrospective chart review was performed for all patients who had undergone surgery and a pre-operative Human Immunodeficiency Virus (HIV) test, between August 2008 and July 2009 at the Eye unit of the Presbyterian Joint Hospital, Ohaozara, Ebonyi State, Nigeria. Data were analyzed for age, sex, type of surgery and HIV status. Frequency, percentage and 95% confidence intervals (CI) were calculated with univariate analysis and the parametric method. RESULTS: A total of 380 cases were reviewed comprised of 228 males and 152 females (M:F= 1.5:1).The mean age of the cohort is 56 years (range, 4 years to 91 years). Fourteen patients (3.7%; 95% confidence interval 1.8 - 5.6) were HIV positive. CONCLUSION: A high HIV sero-prevalence was reported in our study. Infection-control precautionary measures are indicated to minimize risk of HIV transmission to ophthalmic surgeons and allied health-workers.