Three-year findings of the HORIZON trial: a Schlemm canal microstent for pressure reduction in primary open angle glaucoma and cataract

OBJECTIVE: To report 3-year outcomes of the HORIZON study comparing cataract surgery with Hydrus Microstent versus cataract surgery alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Five hundred fifty-six eyes from 556 patients with cataract and POAG treated with ≥ 1 glaucoma medication, washed out diurnal intraocular pressure (DIOP) 22-34 mmHg and no prior incisional glaucoma surgery. METHODS: Following phacoemulsification, eyes were randomized 2:1 to receive a Hydrus® Microstent (Ivantis, Inc.) or no stent. Follow-up included comprehensive eye examinations through 3 years postoperatively. MAIN OUTCOME MEASURES: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. RESULTS: 369 eyes were randomized to microstent treatment (HMS) and 187 to cataract surgery only (CS). Preoperative IOP, medication usage, washed out DIOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 in the HMS group and 17.0 ± 3.4 in the CS group (p=0.85). The number of glaucoma medications was 0.4 ± 0.8 in the HMS group and 0.8 ± 1.0 in the CS group (p<0.001), and 73% of eyes in the HMS group were medication free compared to 48% in the CS group (p<0.001). The HMS group had a higher proportion of eyes with IOP ≤18 mmHg without medications compared to CS (56.2% vs. 34.6%, p<0.001) as well as IOP reduction of at least 20, 30 or 40 percent compared to CS alone. The cumulative probability of incisional glaucoma surgery was lower in the HMS group (0.6% vs. 3.9%, hazard ratio = 0.156, 95% CI 0.031 to 0.773, p=0.020). There was no difference in postoperative corneal endothelial cell loss between groups. There were no procedure or device related serious adverse events resulting in vision loss in either group. CONCLUSIONS: Combined cataract surgery and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtrations surgery than cataract surgery alone at 3 years

Local interactions under switching costs

We study the impact of switching costs on the long-run outcome in 2×2 coordination games played in the circular city model of local interactions. For low levels of switching costs, the predictions are in line with the previous literature and the risk-dominant convention is the unique long-run equilibrium. For intermediate levels of switching costs, the set of long-run equilibria still contain the risk-dominant convention but may also contain conventions that are not risk dominant. The set of long-run equilibria may further be non-monotonic in the level of switching costs, i.e., as switching costs increase the prediction that the risk-dominant convention is the unique long-run equilibrium and the prediction that both conventions are long-run equilibria alternate. Finally, for high levels of switching costs, also non-monomorphic states will be included in the set of long-run equilibria

Self domestication and the evolution of language

We set out an account of how self-domestication plays a crucial role in the evolution of language. In doing so, we focus on the growing body of work that treats language structure as emerging from the process ofcultural transmission. We argue that a full recognition of the importance of cultural transmission fundamentally changes the kind ofquestionswe should be asking regarding the biological basis of language structure. If we think of language structure as reflecting an accumulated set of changes in our genome, then we might ask something like, "What are the genetic bases of language structure and why were they selected?" However, if cultural evolution can account for language structure, then this question no longer applies. Instead, we face the task of accounting for the origin of the traits that enabled that process of structure-creating cultural evolution to get started in the first place. In light of work on cultural evolution, then, the new question for biological evolution becomes, "How did those precursor traits evolve?" We identify two key precursor traits: (1) the transmission of the communication system throughlearning; and (2) the ability to infer thecommunicative intentassociated with a signal or action. We then describe two comparative case studies-the Bengalese finch and the domestic dog-in which parallel traits can be seen emerging followingdomestication. Finally, we turn to the role of domestication in human evolution. We argue that the cultural evolution of language structure has its origin in an earlier process of self-domestication.</p

The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in <i>Plasmodium</i> asexual blood stages

Glycosylation is an important posttranslational protein modification in all eukaryotes. Besides glycosylphosphatidylinositol (GPI) anchors and N-glycosylation, O-fucosylation has been recently reported in key sporozoite proteins of the malaria parasite. Previous analyses showed the presence of GDP-fucose (GDP-Fuc), the precursor for all fucosylation reactions, in the blood stages of Plasmodium falciparum. The GDP-Fuc de novo pathway, which requires the action of GDP-mannose 4,6-dehydratase (GMD) and GDP-L-fucose synthase (FS), is conserved in the parasite genome, but the importance of fucose metabolism for the parasite is unknown. To functionally characterize the pathway we generated a PfGMD mutant and analyzed its phenotype. Although the labelling by the fucose-binding Ulex europaeus agglutinin I (UEA-I) was completely abrogated, GDP-Fuc was still detected in the mutant. This unexpected result suggests the presence of an alternative mechanism for maintaining GDP-Fuc in the parasite. Furthermore, PfGMD null mutant exhibited normal growth and invasion rates, revealing that the GDP-Fuc de novo metabolic pathway is not essential for the development in culture of the malaria parasite during the asexual blood stages. Nonetheless, the function of this metabolic route and the GDP-Fuc pool that is generated during this stage may be important for gametocytogenesis and sporogonic development in the mosquito

Randomized Noninferiority Trial of Direct Selective Laser Trabeculoplasty in Open-Angle Glaucoma and Ocular Hypertension: GLAUrious Study

PURPOSE: Effective glaucoma treatment is limited by nonadherence to medications and access to selective laser trabeculoplasty (SLT). The GLAUrious study compared automated, gonioscopy-free, noncontact, image-guided direct selective laser trabeculoplasty (DSLT) with conventional SLT in open-angle glaucoma (OAG) and ocular hypertension (OHT) to reduce intraocular pressure (IOP). DESIGN: Prospective, multicenter, randomized, controlled, evaluator-masked noninferiority trial. Participants Participants aged ≥ 40 years with OAG or OHT, on 0–3 hypotensive medications at screening, and washout IOP of 22–35 mmHg at 14 centers. METHODS: After washout, 192 participants randomized 1:1 to DSLT (n = 99) or SLT (n = 93). Intraocular pressure was assessed before treatment and through 12 months after the procedure, with washout IOP at baseline and 6 months. Main Outcome Measures Difference between DSLT and SLT in mean IOP change from baseline to 6 months (noninferiority margin, –1.95 mmHg). Exploratory efficacy and safety outcomes were assessed over 12 months. RESULTS: Of 156 participants (81.3%) without major protocol deviations analyzed at 6 months, the mean ± standard error (SE) washout IOP reduction from baseline was 5.5 ± 0.5 mmHg (–20.6%) after DSLT and 6.2 ± 0.5 mmHg (–23.6%) after SLT. The between-group difference (SLT–DSLT) in mean IOP reduction was –0.7 mmHg (95% confidence interval [CI], –2.2 to 0.8 mmHg; P = 0.09 [not significant] for noninferiority). Of 161 participants (83.9%) without major protocol deviations analyzed at 12 months, mean ± SE nonwashout IOP reduction from screening was 3.2 ± 0.4 mmHg (–12.2%) after DSLT and 3.2 ± 0.4 mmHg (–9.4%) after SLT. The between-group difference in mean IOP reduction was 0.01 mmHg (95% CI, –1.1 to 1.1 mmHg; P < 0.001 for noninferiority). Safety profiles were similar between groups, although clinically nonsignificant punctate subconjunctival hemorrhage was more frequent in the DSLT group. Ocular AEs generally were mild and resolved without intervention. CONCLUSIONS: The 6-month primary end point did not achieve statistical noninferiority compared with conventional SLT. Nonetheless, DSLT was well tolerated and provided an effective reduction in IOP that was sustained for 12 months. Failure to demonstrate noninferiority does not prove inferiority; DSLT remains an effective option in the early treatment paradigm and can be considered as a first-line treatment when SLT is not readily accessible. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article

Update on Surgical Techniques Best Practices to Optimize Outcomes Following Gel Stent Implantation

Vanessa Vera,1 Arsham Sheybani,2 Joseph F Panarelli,3 Davinder S Grover,4 James Lee,5 Earl Randy Craven,2 Thomas W Samuelson,6 Iqbal Ike K Ahmed7 1Allergan, an AbbVie company, Irvine, CA, USA; 2Washington University School of Medicine, St Louis, MO, USA; 3Department of Ophthalmology, New York University Langone Health, New York, NY, USA; 4Glaucoma Associates of Texas, Dallas, TX, USA; 5Colorado Eye Institute, Colorado Springs, CO, USA; 6Minnesota Eye Consultants, University of Minnesota, Minneapolis, MN, USA; 7John Moran Eye Center, University of Utah, Salt Lake City, UT, USACorrespondence: James Lee, Colorado Eye Institute, Colorado Springs, CO, 80924, USA, Email [email protected]: The XEN® 45 Glaucoma Treatment System (gel stent; Allergan, an AbbVie company, Irvine, CA, USA) is a minimally invasive bleb-forming surgical device that was originally approved to lower intraocular pressure by diverting the aqueous humor from the anterior chamber to the subconjunctival space (like trabeculectomy) following ab-interno placement. Since approval of the gel stent in multiple countries, the implantation technique has evolved considerably, being performed ab interno or ab externo with open or closed conjunctiva, based on patients’ needs and/or surgeons’ preferences. Additional technical variations that can facilitate gel stent placement and/or improve outcomes have also emerged. This article aims to increase awareness of these developments to facilitate informed decision-making and improve surgical success and outcomes for patients.Keywords: ab interno, ab externo, glaucoma, intraocular pressure, surgical outcomes, XE

Women’s preferences for inpatient and outpatient priming for labour induction: a discrete choice experiment

BACKGROUND In many countries a high proportion of births begin as induced labours. Induction can be lengthy if cervical priming is required prior to induction. This usually occurs as an inpatient, however, an alternative is to allow women to go home after satisfactory fetal monitoring. The aim of this study was to assess the preferences of women for cervical priming for induction of labour in an outpatient or inpatient setting. METHOD A discrete choice experiment (DCE) was conducted alongside a randomised trial of inpatient and outpatient cervical priming (the OPRA trial) in two maternity hospitals in South Australia. 362 participants were included, and women’s preferences for cervical priming for induction of labour were assessed. RESULTS Women were willing to accept an extra 1.4 trips to hospital (2.4 trips total) and a total travel time of 73.3 minutes to be able to return to their own home while waiting for the priming to work. For enhanced inpatient services, women were willing to accept a total travel time of 54.7 minutes to have a private room with private bathroom while waiting for the priming to work. The overall benefit score for outpatient priming was 3.63, 3.59 for enhanced inpatient care and 2.89 for basic inpatient care, suggesting slightly greater preferences for outpatient priming. Preferences for outpatient priming increased when women could return to their own home (compared to other offsite accommodation), and decreased with more trips to hospital and longer travel time. CONCLUSIONS Our results suggest that outpatient priming was slightly more preferred than either enhanced inpatient priming or basic care; these results should be confirmed in different clinical settings. There may be merit in providing women information about both options in the future, as preferences varied according to the characteristics of the services on offer and the sociodemographic background of the woman.Kirsten Howard, Karen Gerard, Pamela Adelson, Robert Bryce, Chris Wilkinson, and Deborah Turnbul

Controversies in the Use of MIGS

Abstract Minimally invasive glaucoma surgery (MIGS) has fulfilled an unmet need in the management of glaucoma. This chapter highlights some controversial issues regarding the use of MIGS in clinical practice, including (1) whether there is sufficient evidence to advocate combining MIGS with cataract surgery over cataract surgery alone, (2) the merits and drawbacks of different approaches to trabecular bypass and canal-based MIGS procedures, (3) the effect of MIGS on endothelial cell loss, (4) suprachoroidal MIGS devices and whether there is still a role for these procedures, and (5) a comparison between subconjunctival MIGS and trabeculectomy. Several questions are still left unanswered and hopefully, further research and more clinical experience with these new technologies will help improve surgical outcomes for patients