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.

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.

Clinical Manifestations, Prognosis, and Vaccination Status of Patients With Rubella Virus-Associated Uveitis.

PURPOSE: To assess the clinical and laboratory manifestations and vaccination status of uveitis patients positive for rubella virus (RV) in aqueous humor and investigate its relationship to Fuchs uveitis syndrome (FUS). METHODS: Retrospective study of all uveitis patients, positive for RV in aqueous humor analysis (polymerase chain reaction [PCR] and/or Goldmann-Witmer coefficient [GWC]) between January 2010 and October 2016 at the ophthalmology departments in the Erasmus Medical Center (Rotterdam) and University Medical Center Utrecht. Outcomes of aqueous analyses of FUS patients during this period were assessed. RESULTS: We included 127 patients (144 eyes) positive for RV in aqueous fluid: 23 (20%) by PCR, 120 (97%) by GWC, and 16 (13%) by both. The average age at first presentation was 37 years. Patients typically complained of blurred vision and exhibited a combination of unilateral anterior uveitis, keratic precipitates, vitritis, and absence of posterior synechiae, but the classical FUS was observed in a minority. The main cause of untreatable visual loss was glaucoma. Cystoid macular edema (CME) before intraocular surgery was not encountered. None of the unilateral cases developed involvement of the other eye. None of the patients was vaccinated against RV. All FUS patients, except 2 (5%), were positive for RV. CONCLUSION: RV-associated uveitis and FUS are not exchangeable. Chronic anterior uveitis, vitritis, early development of cataract, and the absence of posterior synechiae and CME characterize RV-associated uveitis. Almost all FUS cases had documented intraocular RV infection, but only some of the patients with RV-associated uveitis presented with FUS.