Manifestations of intraocular inflammation over time in patients on brolucizumab for neovascular AMD

Purpose To describe the adverse events associated with brolucizumab, in particular the sequence of intraocular inflammation (IOI), retinal vasculitis (RV), and/or retinal vascular occlusion (RO).Methods This was an unmasked post hoc analysis of the randomized HAWK/HARRIER clinical trials. Patients with neovascular AMD in the brolucizumab arms of the trials were included. IOI-related adverse events reported by study investigators were analyzed to determine early signs and the time course of IOI-related adverse events, using a subgroup of patients with definite/probable IOI cases identified in an independent unmasked post hoc review by an external safety review committee. A limited literature review on MI following anti-VEGF therapy was also conducted.Results Among 50 patients with definite/probable IOI cases identified by the safety review committee, 12 had RV or RO adverse events reported by the investigators. For 6 of 12, IOI (other than RV) was reported before RV or RO. The duration from the first IOI adverse event to the first RV or RO adverse event ranged from 16 to 171 days for 5 patients and was 553 days for 1 patient. Four of the 6 patients received >= 1 brolucizumab injection on or after the date of the first IOI adverse event and before the first RV or RO adverse event.Conclusions IOI may precede RV or RO in some patients treated with brolucizumab.Ophthalmic researc

acceptability of nudges as public policy tools : a theoretical and empirical analysis

Aquesta tesi presenta una anàlisi teòrica i empírica de l'acceptabilitat dels nudges com a eines de política pública. La primera part de la tesi discuteix la caracterització dels nudges com a instruments de política pública, considerant qüestions conceptuals, ètiques i teòriques. La tesi revisa la noció original de nudge, les seves bases teòriques i empíriques i les principals crítiques en els dos sentits. Exposant els problemes amb la noció de nudge de Thaler i Sunstein, proposa una definició alternativa del concepte que defensa deixar de banda les connotacions i intencions normatives i centrar-se en el seu valor pràctic com a eina de política pública. La segona part inclou tres estudis empírics d'actituds cap als nudges: una enquesta representativa (n = 617, i = 3,88) de l'acceptabilitat pública dels nudges a Espanya, i dos estudis experimentals que exploren l'acceptabilitat de dos tipus de nudges, els nudges automàtics, que són menys perceptibles i funcionen sense deliberació o consciència, i els nudges reflexius que són perceptibles, inclouen deliberació i produeixen una resposta conscient. La part empírica aborda les qüestions discutides en el debat teòric i emfatitza que la discussió sobre l'acceptabilitat dels nudges en política pública ha de considerar la seva acceptabilitat pública i, en particular, quins nudges es prefereixen i en quins contextos s'accepta la seva implementació. Els resultats indiquen tres qüestions principals. En primer lloc, l'acceptabilitat pública dels nudges és alta, els ciutadans aproven l'ús de diferents nudges en diferents àmbits i no s'oposen categòricament a la seva implementació. En segon lloc, el tipus de nudge és important. Les persones reconeixen diferències entre nudges i tendeixen a preferir els nudges reflexius als nudges automàtics. Tanmateix, els resultats dels tres estudis indiquen que l'oposició a la implementació de nudges automàtics no és categòrica i es recolza el seu ús en diversos casos. En tercer lloc, l'acceptabilitat dels nudges automàtics depèn del context en què s'apliquen; les persones donen suport al seu ús quan estan d'acord amb el seu objectiu i quan afecten decisions en àmbits de baix risc. Per contra, s'oposen a la seva implementació quan afecten decisions en dominis d'alt risc, per exemple, quan es fan servir en decisions que involucren assumptes sensibles o morals o decisions que involucren pèrdues econòmiques. En general, la tesi explora arguments a favor i en contra de l'ús de nudges i ofereix idees sobre com poden ser eines útils i acceptables per a la formulació de polítiques públiques.Esta tesis presenta un análisis teórico y empírico de la aceptabilidad de los nudges como herramientas de política pública. La primera parte de la tesis discute la caracterización de los nudges como instrumentos de política pública, con atención a cuestiones conceptuales, éticas y teóricas. La tesis revisa la noción original de nudge, sus bases teóricas y empíricas y las principales críticas en ambos sentidos. Exponiendo los problemas con la noción de nudge de Thaler y Sunstein, propone una definición alternativa del concepto que aboga por dejar de lado las connotaciones e intenciones normativas y centrarse en su valor práctico como herramienta de política pública. La segunda parte incluye tres estudios empíricos de actitudes hacia los nudges: una encuesta representativa (n = 617, e = 3,88) de la aceptabilidad pública de los nudges en España, y dos estudios experimentales que exploran la aceptabilidad de dos tipos de nudges, los nudges automáticos, que son menos perceptibles y funcionan sin deliberación o conciencia, y los nudges reflexivos que son perceptibles, incluyen deliberación y producen una respuesta consciente. La parte empírica aborda las cuestiones discutidas en el debate teórico y enfatiza que la discusión sobre la aceptabilidad de los nudges en política pública debe considerar su aceptabilidad pública y, en particular, qué nudges se prefieren y en qué contextos se acepta su implementación. Los resultados indican tres cuestiones principales. En primer lugar, la aceptabilidad pública de los empujones es alta, los ciudadanos aprueban el uso de diferentes nudges en diferentes ámbitos y no se oponen categóricamente a su implementación. En segundo lugar, el tipo de nudge es importante. Las personas reconocen diferencias entre nudges y tienden a preferir los nudges reflexivos a los nudges automáticos. No obstante, los resultados de los tres estudios indican que la oposición a la implementación de nudges automáticos no es categórica y, en varios casos, se apoya su uso. En tercer lugar, la aceptabilidad de los nudges automáticos depende del contexto en el que se apliquen; las personas apoyan su uso cuando están de acuerdo con su objetivo y cuando afectan decisiones en ámbitos de bajo riesgo. Por el contrario, su uso no está respaldado cuando afectan decisiones en dominios de alto riesgo, como decisiones que involucran asuntos sensibles o morales o decisiones que involucran pérdidas económicas. En general, la tesis explora argumentos a favor y en contra del uso de nudges y ofrece ideas sobre cómo los nudges pueden ser herramientas útiles y aceptables para la formulación de políticas públicas.This thesis is a theoretical and empirical analysis of the acceptability of nudges as policy tools. The first part of the thesis discusses the characterisation of nudges as a policy instrument, paying attention to conceptual, ethical and theoretical issues. The thesis looks at the original notion of nudges, their theoretical and empirical bases and the main criticisms of both dimensions. It goes on to outline the problems with Thaler and Sunstein's notion of nudges and proposes an alternative understanding of nudges, advocating dropping the normative connotations of nudges, and focusing on their practical value as a policy tool. The second part includes three empirical studies on attitudes towards nudges: a nationally representative survey (n= 617, e=3.88) of the public acceptability of nudges in Spain, and two experimental studies that explore the acceptability of two types of nudges, automatic nudges that are less noticeable, work with no deliberation and awareness, and reflective nudges that are noticeable, work by engaging deliberation and produce a more reflective response. The empirical part addresses some of the concerns discussed in the theoretical debate and emphasises that the discussion on the acceptability of nudges as policy tools should include considerations about whether people like nudges, which nudges they prefer and the contexts in which they accept their implementation. The results outline three main themes. Firstly, the public acceptability of nudges is high, people favour the use of different nudges applied to both pro-self and pro-social domains and the indication is that people do not categorically oppose nudges. Secondly, the type of nudge is important. People recognise differences between nudges and tend to preferer reflective nudges to automatic nudges. At the same time, the findings in the three studies indicate that people do not categorically oppose the implementation of automatic nudges and support their use in several cases. Thirdly, the acceptability of automatic nudges depends on the context in which they are applied; people support their use when they agree with the aim and when they affect behaviour in low-stake domains. By contrast, their use is not supported when they affect decisions in high-stake domains, such as decisions that involve sensitive or moral issues or decisions that involve economic losses. Overall, the thesis explores arguments in favour of and against nudges and offers ideas and conclusions to give an idea of how nudges could be useful and acceptable tools for policymaking.Universitat Autònoma de Barcelona. Programa de Doctorat en Sociologi

Visual Function Decline Resulting from Geographic Atrophy: Results from the Chroma and Spectri Phase 3 Trials

PurposeTo assess visual function outcomes to 48 weeks in patients with bilateral geographic atrophy (GA) secondary to age-related macular degeneration included in 2 interventional clinical trials: relationship to baseline lesion size, outcomes by baseline lesion characteristic subgroups, and correlation of visual function outcomes with GA area.DesignThe Chroma and Spectri studies (ClinicalTrials.gov identifiers, NCT02247479 and NCT02247531, respectively) were identically designed phase 3, double-masked, multicenter, randomized, sham injection-controlled clinical trials that evaluated intravitreal lampalizumab in GA.ParticipantsEligible patients were 50 years of age or older with well-demarcated bilateral GA (lesion size, 1–7 disc areas) without evidence of or previous treatment for choroidal neovascularization in either eye and best-corrected visual acuity (BCVA) letter score of 49 letters or more (≥1 GA lesion within 250 μm of foveal center if BCVA ≥79 letters).MethodsPatients (pooled n = 1881) were randomized 2:1:2:1 to lampalizumab every 4 weeks, sham every 4 weeks, lampalizumab every 6 weeks, or sham every 6 weeks. Sham arms were pooled for analysis.Main Outcome MeasuresFunctional end points included change in BCVA from baseline to week 48, low-luminance visual acuity, mesopic microperimetry (number of absolute scotomatous points, mean macular sensitivity), binocular and monocular maximum reading speed, and 2 validated patient-reported outcome measures: Functional Reading Independence Index and 25-item National Eye Institute Visual Function Questionnaire.ResultsEnlargement of GA area, approximately 2 mm2/year on average across all treatment groups in each study, was accompanied by overall deterioration in all functional end points. No statistically significant differences were found between lampalizumab or sham arms for changes from baseline in functional assessment scores. Of visual function tests, only microperimetry outcomes were correlated moderately with GA lesion area when assessed cross-sectionally at baseline and week 48.ConclusionsChroma and Spectri provide a unique data set of functional end points in GA that are relevant for future clinical trials. Patients with bilateral GA experienced a consistent decline in visual function over 48 weeks, but measures of visual function were not correlated strongly with GA lesion area. It is not possible to predict visual function outcomes from GA lesion size

Intravitreal aflibercept injection for neovascular age-related macular degeneration: Ninety-six-week results of the VIEW studies

Purpose To determine efficacy and safety of intravitreal aflibercept in patients with neovascular age-related macular degeneration (AMD) during a second year of variable dosing after a first-year fixed-dosing period. Design Two randomized, double-masked, active-controlled, phase 3 trials. Participants Two thousand four hundred fifty-seven patients with neovascular AMD. Methods From baseline to week 52, patients received 0.5 mg intravitreal ranibizumab every 4 weeks (Rq4), 2 mg aflibercept every 4 weeks (2q4), 0.5 mg aflibercept every 4 weeks (0.5q4), or 2 mg aflibercept every 8 weeks (2q8) after 3 monthly injections. During weeks 52 through 96, patients received their original dosing assignment using an as-needed regimen with defined retreatment criteria and mandatory dosing at least every 12 weeks. Main Outcome Measures Proportion of eyes at week 96 that maintained best-corrected visual acuity (BCVA; lost <15 letters from baseline); change from baseline in BCVA. Results Proportions of eyes maintaining BCVA across treatments were 94.4% to 96.1% at week 52 and 91.5% to 92.4% at week 96. Mean BCVA gains were 8.3 to 9.3 letters at week 52 and 6.6 to 7.9 letters at week 96. Proportions of eyes without retinal fluid decreased from week 52 (60.3% to 72.4%) to week 96 (44.6% to 54.4%), and more 2q4 eyes were without fluid at weeks 52 and 96 than Rq4 eyes (difference of 10.4% [95% confidence interval {CI}, 4.9-15.9] and 9.0% [95% CI, 3.0-15.1]). Patients received on average 16.5, 16.0, 16.2, and 11.2 injections over 96 weeks and 4.7, 4.1, 4.6, and 4.2 injections during weeks 52 through 96 in the Rq4, 2q4, 0.5q4, and 2q8 groups, respectively. The number of injections during weeks 52 through 96 was lower in the 2q4 and 2q8 groups versus the Rq4 group (differences of -0.64 [95% CI, -0.89 to -0.40] and -0.55 [95% CI, -0.79 to -0.30]; P < 0.0001, post hoc analysis). Incidences of Antiplatelet Trialists' Collaboration-defined arterial thromboembolic events were similar across groups (2.4% to 3.8%) from baseline to week 96. Conclusions All aflibercept and ranibizumab groups were equally effective in improving BCVA and preventing BCVA loss at 96 weeks. The 2q8 aflibercept group was similar to ranibizumab in visual acuity outcomes during 96 weeks, but with an average of 5 fewer injections. Small losses at 96 weeks in the visual and anatomic gains seen at 52 weeks in all arms were in the range of losses commonly observed with variable dosing. © 2014 by the American Academy of Ophthalmology