Exfoliation syndrome (XFS) is the commonest known risk factor for secondary glaucoma and a significant cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A have been previously associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results between populations, and to identify new variants associated with XFS. We identified a rare, protective allele at LOXL1 (p.407Phe, OR = 25, P =2.9 × 10−14) through deep resequencing of XFS cases and controls from 9 countries. This variant results in increased cellular adhesion strength compared to the wild-type (p.407Tyr) allele. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10−8). Index variants at the new loci map to chromosomes 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS, and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.

Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide for which 15 disease-associated loci had been discovered. Among them, only 5 loci have been associated with POAG in Asians. We carried out a genome-wide association study and a replication study that included a total of 7378 POAG cases and 36 385 controls from a Japanese population. After combining the genome-wide association study and the two replication sets, we identified 11 POAG-associated loci, including 4 known (CDKN2B-AS1, ABCA1, SIX6 and AFAP1) and 7 novel loci (FNDC3B, ANKRD55-MAP3K1, LMX1B, LHPP, HMGA2, MEIS2 and LOXL1) at a genome-wide significance level (P < 5.0×10-8), bringing the total number of POAG-susceptibility loci to 22. The 7 novel variants were subsequently evaluated in a multiethnic population comprising non-Japanese East Asians (1008 cases, 591 controls), Europeans (5008 cases, 35 472 controls) and Africans (2341 cases, 2037 controls). The candidate genes located within the new loci were related to ocular development (LMX1B, HMGA2 and MAP3K1) and glaucoma-related phenotypes (FNDC3B, LMX1B and LOXL1). Pathway analysis suggested epidermal growth factor receptor signaling might be involved in POAG pathogenesis. Genetic correlation analysis revealed the relationships between POAG and systemic diseases, including type 2 diabetes and cardiovascular diseases. These results improve our understanding of the genetic factors that affect the risk of developing POAG and provide new insight into the genetic architecture of POAG in Asians.

The high prevalence of glaucoma (7.3%) in the Akinyele district in southwestern Nigeria is comparable with those in predominantly black populations in the Akwapim-South district of Ghana and Barbados. Primary open angle glaucoma remains the most prevalent form of glaucoma.

Purpose:To describe the factors that determine the utilization of eye care services in a rural community in South-Western Nigeria.Methods:A descriptive cross-sectional survey using a multistage sampling technique was conducted. The main outcome measure was self-reported previous consultation of an orthodox medical facility for eye care.Results:The study sample included 643 participants. Only 122 (19%) respondents had previously visited orthodox facilities in search of eye care and 24% of those with presenting visual acuity <6/18 had sought eye care. Characteristics associated with previous utilization of eye care services were age of =70 years (odds ratio [OR] ≥ 1.7, P = 0.02); male gender (OR = 1.5, P = 0.04); literacy (OR = 1.7, P = 0.007); and residing close to an eye care facility (OR = 2.8, P < 0.001). Blind respondents were three times more likely to seek eye care (P < 0.001). Regression analysis revealed that factors associated with increased likelihood of utilization of eye care services included age ≥70 years; literacy; residence close to an eye facility; being diabetic or hypertensive; history of ocular symptoms, and blindness.Conclusions:These findings suggest that a significant proportion (75%) of adults in the study area are not utilizing eye care services and that blindness is an important determinant of utilization of eye care services. Health education and awareness campaigns about the importance and benefits of seeking eye care early, and the provision of community-based eye care programs are essential to boost the uptake of eye care services in this community as well as other rural areas of West Africa.