RESUMO
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 14â¯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 14â¯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.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , População Negra/genética , Estudo de Associação Genômica Ampla , Glaucoma de Ângulo Aberto/etnologia , Glaucoma de Ângulo Aberto/genética , Polimorfismo de Nucleotídeo Único , Idoso , Peptídeos beta-Amiloides/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Imuno-Histoquímica , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
AIMS:: To compare the efficacy and safety of trabeculectomy with Ologen versus Mitomycin C in primary glaucoma. MATERIALS AND METHODS:: This is a prospective study of patients aged 18 years and above, diagnosed with primary glaucoma randomised to having trabeculectomy with Ologen or Mitomycin C. The primary outcome measure was success of trabeculectomy defined as intraocular pressure >5 mmHg but ≤21 mmHg. Complete success was defined as intraocular pressure achieved without anti-glaucoma medication and qualified success was defined as intraocular pressure achieved with additional anti-glaucoma medication. RESULTS:: At the end of 12 months follow-up, the postoperative mean intraocular pressure in the Ologen group was 12.8 ± 1.6 mmHg and 13.4 ± 2.2 mmHg in the Mitomycin C group. The Ologen group achieved complete success in 86.5% and qualified success in 13.5% of the patients, while the Mitomycin C group achieved complete and qualified success in 85.5% and 14.5%, respectively. There was no statistically significant difference in the success rate of both the groups ( p = 0.57). Furthermore, no significant intraocular pressure difference was noted between the two groups at the end of 12 months follow-up ( p = 0.14). CONCLUSION:: Trabeculectomy augmented with Ologen appeared to be as successful and safe as trabeculectomy augmented with Mitomycin C, with no reported adverse reaction to Ologen.