Vogt-Koyanagi-Harada (VKH) disease is a systemic inflammatory disorder that affects pigment cell-containing organs such as the eye (e.g., chronic and/or recurrent granulomatous panuveitis). While the exact etiology and pathogenic mechanism of VKH disease are unclear, HLA-DR4 alleles have been documented to be strongly associated with VKH disease in various ethnic groups. Recently, a genome-wide association study (GWAS) found two new genetic risk factors (IL23R-C1orf141 and ADO-ZNF365-EGR2) in a non-HLA region from a Han Chinese population. In this study, we replicated these GWAS findings in a Japanese population. A total of 1,643 Japanese samples (380 cases with VKH disease and 1,263 healthy controls) were recruited. We assessed four single nucleotide polymorphisms (SNPs) shown in previous GWAS: rs78377598 and rs117633859 in IL23R-C1orf141, and rs442309 and rs224058 in ADO-ZNF365-EGR2. A significant allelic association with VKH disease was observed for all of the four SNPs (rs78377598: p c = 0.0057; rs117633859: p c = 0.0017; rs442309: p c = 0.021; rs224058: p c = 0.035). In genotypic association analysis, the minor alleles of IL23R-C1orf141 rs78377598 and rs117633859 had the strongest association with disease susceptibility under the additive model (p c = 0.0075 and p c = 0.0026,

Introduction This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. Methods A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. Results BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC ( P < 0.0001). More patients preferred BTFC ( P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. Conclusion As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. Trial Registration Number jRCTs051190125.

This multicentre, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed-combinations 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for eight weeks. These patients were then crossed over to the alternative treatment arm for another eight weeks. The intraocular pressure (IOP) reduction (primary outcome), adverse event occurrence, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patients’ interviews. BTFC instillation for eight weeks resulted in IOP reduction by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P <0.0001, mixed-effects model). Although adverse effects were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC instillation (P <0.0001). More patients preferred BTFC (P <0.0001) over DTFC, as the former caused minimal or no eye irritation. As BTFC offers better tolerability than DTFC with comparable IOP reduction, we recommend it as an alternative in patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy.