Baerveldt implant for secondary glaucoma due to iris melanoma

Annelie N Tan1, Juliette GMM Hoevenaars1, Carroll AB Webers1, Bertil Damato2, Henny JM Beckers11University Eye Clinic, Maastricht, The Netherlands; 2Ocular Oncology Service Royal Liverpool University Hospital, Liverpool, United KingdomBackground: Proton beam therapy (PBT) is effective in the treatment of iris melanoma. Reported complications after PBT are radiation-induced cataract and raised intraocular pressure (IOP). Filtering glaucoma surgery has generally been avoided because of fears of seeding.Case report: A 37-year-old man presented with a self-discovered, pigmented lesion on his right iris. Four years later, the pigmented lesion was diagnosed as an iris melanoma, because of documented growth. The patient was treated with PBT but developed secondary glaucoma one month later. The IOP could not be controlled despite maximal medical therapy and selective laser trabeculoplasty (SLT). Finally, Baerveldt implant surgery was performed, resulting in an IOP lowering to 10 mmHg and stabilization of the glaucomatous visual field loss.Conclusion: Our case demonstrates that Baerveldt implant surgery is a reasonable therapy for glaucoma following successful radiotherapy of iris melanoma.Keywords: iris melanoma, proton beam therapy, secondary glaucoma, Baerveldt implant surger

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

Addressing climate change with behavioral science: a global intervention tournament in 63 countries

Effectively reducing climate change requires marked, global behavior change. However, it is unclear which strategies are most likely to motivate people to change their climate beliefs and behaviors. Here, we tested 11 expert-crowdsourced interventions on four climate mitigation outcomes: beliefs, policy support, information sharing intention, and an effortful tree-planting behavioral task. Across 59,440 participants from 63 countries, the interventions’ effectiveness was small, largely limited to nonclimate skeptics, and differed across outcomes: Beliefs were strengthened mostly by decreasing psychological distance (by 2.3%), policy support by writing a letter to a future-generation member (2.6%), information sharing by negative emotion induction (12.1%), and no intervention increased the more effortful behavior—several interventions even reduced tree planting. Last, the effects of each intervention differed depending on people’s initial climate beliefs. These findings suggest that the impact of behavioral climate interventions varies across audiences and target behaviors

Polygenic Risk Modelling for Prediction of Epithelial Ovarian Cancer Risk

Funder: Funding details are provided in the Supplementary MaterialAbstractPolygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally-efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestry; 7,669 women of East Asian ancestry; 1,072 women of African ancestry, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestry. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38(95%CI:1.28–1.48,AUC:0.588) per unit standard deviation, in women of European ancestry; 1.14(95%CI:1.08–1.19,AUC:0.538) in women of East Asian ancestry; 1.38(95%CI:1.21-1.58,AUC:0.593) in women of African ancestry; hazard ratios of 1.37(95%CI:1.30–1.44,AUC:0.592) in BRCA1 pathogenic variant carriers and 1.51(95%CI:1.36-1.67,AUC:0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.</jats:p

Outcomes of severe uveitic glaucoma treated with Baerveldt implant: can blindness be prevented?

Purpose\u3cbr/\u3eTo evaluate long-term outcomes on efficacy and safety of severe uveitic glaucoma treated with a Baerveldt glaucoma implant (BGI).\u3cbr/\u3eMethods\u3cbr/\u3eA retrospective study of 47 eyes of 47 patients with uveitic glaucoma treated by a BGI between September 2002 and September 2015. Main outcome measures were intraocular pressure (IOP), number of glaucoma medications, course of the uveitis, visual acuity (VA) and complications.\u3cbr/\u3eResults\u3cbr/\u3eMean IOP dropped from 30.6 ± 8.1 mmHg with 3.6 ± 1.1 glaucoma medications at baseline to 10.6 ± 4.3 mmHg with 1.0 ± 1.3 glaucoma medications after a mean follow-up of 63.6 ± 43.1 months. In the majority of cases, IOP remained stable during follow-up. However, especially in several patients with viral uveitis, episodes with IOP peaks were observed during a flare-up despite a functioning implant. These peaks remained below preoperative levels. During follow-up, 16 patients (34%) experienced a clinically significant VA loss, mainly because of late-stage glaucoma or hypotony maculopathy. Early postoperative complications were transient choroidal effusion (n = 5), shallow/flat anterior chamber (n = 4), hyphaema (n = 2) and suprachoroidal haemorrhage (n = 1). The most important late postoperative complication was hypotony maculopathy (n = 5), three of these in juvenile idiopathic arthritis (JIA) patients.\u3cbr/\u3eConclusion\u3cbr/\u3eThe BGI is an effective and safe treatment for patients with refractive secondary glaucoma due to uveitis. In a majority of patients, VA remains stable and a low and stable IOP is maintained over time with an acceptable number of complications. In particular, patients with viral uveitis and glaucoma should be closely monitored for IOP peaks that may occur during episodes of a flare-up of uveitis, whereas at the other end of the spectrum, patients with JIA seem much more prone to hypotony maculopathy.\u3cbr/\u3