Specificity of the STAT4 Genetic Association for Severe Disease Manifestations of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a genetically complex disease with heterogeneous clinical manifestations. A polymorphism in the STAT4 gene has recently been established as a risk factor for SLE, but the relationship with specific SLE subphenotypes has not been studied. We studied 137 SNPs in the STAT4 region genotyped in 4 independent SLE case series (total n = 1398) and 2560 healthy controls, along with clinical data for the cases. Using conditional testing, we confirmed the most significant STAT4 haplotype for SLE risk. We then studied a SNP marking this haplotype for association with specific SLE subphenotypes, including autoantibody production, nephritis, arthritis, mucocutaneous manifestations, and age at diagnosis. To prevent possible type-I errors from population stratification, we reanalyzed the data using a subset of subjects determined to be most homogeneous based on principal components analysis of genome-wide data. We confirmed that four SNPs in very high LD (r2 = 0.94 to 0.99) were most strongly associated with SLE, and there was no compelling evidence for additional SLE risk loci in the STAT4 region. SNP rs7574865 marking this haplotype had a minor allele frequency (MAF) = 31.1% in SLE cases compared with 22.5% in controls (OR = 1.56, p = 10−16). This SNP was more strongly associated with SLE characterized by double-stranded DNA autoantibodies (MAF = 35.1%, OR = 1.86, p<10−19), nephritis (MAF = 34.3%, OR = 1.80, p<10−11), and age at diagnosis<30 years (MAF = 33.8%, OR = 1.77, p<10−13). An association with severe nephritis was even more striking (MAF = 39.2%, OR = 2.35, p<10−4 in the homogeneous subset of subjects). In contrast, STAT4 was less strongly associated with oral ulcers, a manifestation associated with milder disease. We conclude that this common polymorphism of STAT4 contributes to the phenotypic heterogeneity of SLE, predisposing specifically to more severe disease

Diode laser cyclophotocoagulation in refractory glaucoma: Comparison between pediatric and adult glaucomas

OBJECTIVE: To evaluate the outcome of contact transscleral diode laser cyclophotocoagulation (CTDC) in eyes with advanced glaucoma and to compare the efficacy in pediatric and adult patients

Ocular involvement in primary antiphospholipid syndrome - Ocular involvement in primary APS

The purpose of this study is to evaluate the ocular findings in patients with the primary antiphospholipid syndrome (APS). Patients and methods: Twenty-two patients (44 eyes) with primary APS (17 women, 5 men) were examined. All patients were younger than 50 years (median age; 37.5 years). In 18 patients, fundus flourescein angiography was performed in addition to the ophthalmologic examination. Results: Sixteen patients (72.7%) described visual symptoms. Anterior segment was normal in 19 patients (86.4%). Posterior segment abnormalities were observed in 15 patients (68.2%). Venous dilatation and tortuosity were the most common ocular findings. Retinal vascular occlusive disease was detected in 5 patients (22.7%). Flourescein angiography abnormalities were noted in 14 of the 18 patients (77.8%). The most common angiographic finding was pigment epithelial window defects. Conclusions: Our results indicate that posterior eye segment involvement is relatively common in the primary APS. It also seems that the screening for APS is important in young patients with retinal vascular occlusion, especially in those without conventional risk factors

Prevalence of factor V Leiden in patients with retinal vein occlusion

Purpose: Factor V Leiden mutation is a common genetic defect associated with a tendency to venous thrombosis. The aim of this study was to evaluate the prevalence of factor V Leiden in patients with retinal vein occlusion (RVO)