Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size.

Macular spectral domain optical coherence tomography findings in Tanzanian endemic optic neuropathy.

Bilateral optic neuropathy in Dar es Salaam is now considered endemic and is estimated to affect 0.3-2.4% of young adults. The condition is characterized by a subacute bilateral loss of central vision of unknown aetiology. Findings of spectral domain optical coherence tomography have not previously been reported for these patients. All patients diagnosed with endemic optic neuropathy over a 2-year period at the Muhimbili National Hospital underwent spectral domain optical coherence tomography macular imaging. Scans were graded qualitatively for severity of retinal nerve fibre layer loss as well as the presence of microcystic macular changes, which have not previously been described in this condition. Of the 128 patients included (54.7% male; median age 20 years), severe retinal nerve fibre layer loss was found in 185 eyes (74.0%). There was full concordance in retinal nerve fibre layer thickness between the two eyes in 113 (91.1%) patients. Microcystic macular spaces were found in 16 (12.5%) patients and were bilateral in nine (7.0%) individuals. These changes were typically more prominent in the nasal than the temporal macula, predominantly involving the inner nuclear layer, and often occurred in an annular configuration that was evident on en face infra-red imaging, though not discernible on colour fundus photography or clinically. All patients with microcystic macular changes had severe thinning of the retinal nerve fibre layer (P = 0.02). Four patients in whom cystic spaces were demonstrated had sequential scans, and there was no detectable alteration in the configuration of these changes over a period of up to 16 months. This is the first study to document optical coherence tomography findings in endemic optic neuropathy. We have observed symmetrical severe loss of the caeco-central projection (papillomacular bundle) with otherwise well-preserved macular architecture. Also, we have observed microcystic retinal changes in a significant proportion of patients, which were associated with severe retinal nerve fibre layer loss. Similar changes have recently been reported from optical coherence tomography images of patients with multiple sclerosis, relapsing isolated optic neuritis, dominant optic atrophy, Leber's hereditary optic neuropathy and a patient with a chronic compressive optic neuropathy, supporting the hypothesis that this may be a non-specific phenomenon secondary to ganglion cell death. The correspondence of the changes to an annulus discernible on infra-red en face imaging, but not using other conventional retinal imaging techniques highlights the potential usefulness of this modality.

Differences in clinical presentation of primary open-angle glaucoma between African and European populations.

PURPOSE: Primary open-angle glaucoma (POAG) has been reported to occur more frequently in Africans, and to follow a more severe course compared to Europeans. We aimed to describe characteristics of POAG presentation and treatment across three ethnic groups from Africa and one from Europe. METHODS: We ascertained 151 POAG patients from South African Coloured (SAC) and 94 South African Black (SAB) ethnicity from a university hospital in South Africa. In Tanzania, 310 patients were recruited from a university hospital and a referral hospital. In the Netherlands, 241 patients of European ancestry were included. All patients were over 35 years old and had undergone an extensive ophthalmic examination. Patients were diagnosed according to the ISGEO criteria. A biogeographic ancestry analysis was performed to estimate the proportion of genetic African ancestry (GAA). RESULTS: The biogeographic ancestry analysis showed that the median proportion of GAA was 97.6% in Tanzanian, 100% in SAB, 34.2% in SAC and 1.5% in Dutch participants. Clinical characteristics at presentation for Tanzanians, SAB, SAC and Dutch participants, respectively: mean age: 63, 57, 66, 70 years (p < 0.001); visual acuity in the worse eye: 1.78, 1.78, 0.3, 0.3 LogMAR (p < 0.001); maximum intraocular pressure of both eyes: 36, 34, 29, 29 mmHg (panova  < 0.001); maximum vertical cup to disc ratio (VCDR) of both eyes: 0.90, 0.90, 0.84, 0.83 (p < 0.001); mean central corneal thickness: 506, 487, 511, 528 µm (p < 0.001). Fourteen percent of Tanzanian patients presented with blindness (<3/60 Snellen) in the better eye in contrast to only 1% in the Dutch. CONCLUSION: In this multi-ethnic comparative study, Sub-Saharan Africans present at a younger age with lower visual acuity, higher IOP, larger VCDR, than SAC and Dutch participants. This indicates the more progressive and destructive course in Sub-Saharan Africans.

Hypertensive retinopathy and associated factors among nondiabetic chronic kidney disease patients seen at a tertiary hospital in Tanzania: a cross-sectional study.

Background: Hypertensive retinopathy is a known marker of cardiovascular disease, and among unselected patients with chronic kidney disease (CKD) more severe retinopathy has been associated with lower estimated glomerular filtration rate (eGFR). This association has, however, not been widely studied among nondiabetic hypertensive patients with CKD, especially in sub-Saharan Africa. We aimed to determine the prevalence and severity of hypertensive retinopathy and its relationship with eGFR among nondiabetic CKD patients seen at Muhimbili National Hospital in Dar es Salaam, Tanzania. Methods: A hospital-based cross-sectional study was conducted among nondiabetic CKD adult (≥18 years) patients with hypertension. A structured questionnaire was used to record patients' demographic characteristics and their cardiovascular risk profile. eGFR was calculated using the Modification of Diet in the Renal Disease (MDRD) equation and only patients with CKD stage 3 or more were enrolled in the study. Grading of retinopathy was done using the Keith-Wagener classification. Results: In total, 224 patients fulfilled the inclusion criteria and were enrolled. Their mean age was 45.8±14.1 years, and 59.4% were men. The proportions of patients with stage 3, 4, and 5 CKD were 21.4%, 19.6%, and 58.9%, respectively. Hypertensive retinopathy was present in 157 (70.1%) patients and the proportions with grade I, grade II, grade III, and grade IV retinopathy were 17.9%, 18.8%, 19.6%, and 13.8%, respectively. The severity of retinopathy increased with decreasing levels of eGFR, and in multivariate logistic regression analysis, factors found to be independently associated with ≥grade II hypertensive retinopathy were more severe CKD, higher hypertension grades, and alcohol use, all p<0.05. Conclusion: The prevalence of hypertensive retinopathy is high among nondiabetic CKD patients seen at a tertiary hospital in Tanzania and is independently associated with CKD severity. Retinopathy grade can be used as a marker of CKD severity among these patients.

Distribution of corneal spherical aberration in a Tanzanian population.

PURPOSE: To investigate the distribution of corneal spherical aberration (SA) in Tanzanian people of African descent, and to examine the correlation between corneal SA and ocular parameters. DESIGN: Cross-sectional population-based study. METHODS: Residents aged 40 years and older in three villages in the Mkuranga district in Tanzania were enlisted as study participants. Corneal higher-order aberrations (HOAs) for the right eye were measured with a wavefront analyzer (KR-1W, Topcon) and calculated for the central 6.0-mm zone. Corneal curvature radius (CR), corneal astigmatism, and axial length (AL) were also measured and their correlation with corneal SA was assessed. RESULTS: The right eyes of 657 participants (336 male, 321 female) were analyzed. The mean age of the subjects was 57.2 ± 10.3 years (mean ± SD). The mean corneal SA (Zernike spherical aberration coefficient C40) was 0.188 ± 0.095 µm (-0.242 to 0.613). The SAs in about three-quarters of all subjects were between 0.10 and 0.30 µm. The root mean squares of total corneal HOAs and the third- and fourth-order aberrations were 0.629 ± 0.250 µm, 0.539 ± 0.236 µm, and 0.269 ± 0.110 µm, respectively. Corneal SA showed weak significant correlations with CR (Spearman's rank correlation coefficient, r = -0.177, p < 0.001), corneal astigmatism (r = -0.142, p < 0.001), AL (r = -0.168, p < 0.001), and age (r = -0.085, p < 0.05). CONCLUSIONS: This finding may be beneficial for selecting aspheric intraocular lens in this population.

Survey on acute and chronic complications in children and adolescents with type 1 diabetes at Muhimbili National Hospital in Dar es Salaam, Tanzania.

OBJECTIVE: The purpose of this study was to assess glycemic control and complications of type 1 diabetes in children and adolescents in Tanzania. RESEARCH DESIGN AND METHODS: This demographic and clinical survey included 99 children aged between 5 and 18 years attending Muhimbili National Hospital Clinic for Diabetes. A structured questionnaire was used for evaluating socioeconomic data and for estimation of the prevalence of acute complications occurring over the last 6 months. The prevalences of retinopathy and diabetic nephropathy were determined by fundus ophthalmoscopy and by microalbuminuria, respectively. RESULTS: All of these children were treated with a conventional insulin regimen. The mean +/- SD duration of diabetes was 4.76 +/- 3.58 years. Only 1 child (1%) had good glycemic control (A1C <7.5%), 60 children (60.6%) had moderate glycemic control (A1C 7.5-10%), 14 children (14.1%) had poor glycemic control (A1C >10-12.5%), and 24 children (24.2%) had very poor glycemic control (A1C >12.5%). At onset of diabetes, 75% of children presented with diabetic ketoacidosis (DKA); 89 children (89.80%) had at least one episode of DKA, and 55 children (55.67%) had symptomatic hypoglycemic episodes. Microalbuminuria was present in 29 (29.3%) and retinopathy in 22 (22.68%) children. CONCLUSIONS: Although there are some methodological limitations, this survey highlights the difficulties of achieving good metabolic control and the high prevalence of acute and chronic complications in Tanzanian children with type 1 diabetes. These results clearly show that major efforts are needed to improve quality of care in children with type 1 diabetes in Tanzania.