Reliability of Semiautomated Kinetic Perimetry (SKP) and Goldmann Kinetic Perimetry in Children and Adults With Retinal Dystrophies.

PurposeTo investigate the precision of visual fields (VFs) from semiautomated kinetic perimetry (SKP) on Octopus 900 perimeters, for children and adults with inherited retinal degenerations (IRDs). Goldmann manual kinetic perimetry has long been used in the diagnosis and follow-up of these patients, but SKP is becoming increasingly common. Octopus VFs (OVFs) and Goldmann VFs (GVFs) were both mapped on two occasions.MethodsNineteen females and 10 males with IRDs were tested on OVFs and GVFs, with two targets per test (V4e and one smaller target). Tests were performed in the same (randomized) order at two visits about 1 week apart. The VFs were digitized to derive isopter solid angles. Comparisons, within and between visits, were performed with paired t-tests and Bland-Altman plots.ResultsMedian age was 20 years (range, 7-70; 10 participants aged ≤17 years old). There were no significant differences in solid angles between OVFs and GVFs (P ≥ 0.06) or between the two visits' solid angles on either perimeter (P ≥ 0.30). Between-visit test-retest variability for GVFs and OVFs was similar (P ≥ 0.73), with median values of approximately 9% to 13%. Overall variability was lower for children than adults (medians of 7.5% and 12.8%, respectively).ConclusionsOctopus SKP and Goldmann perimetry produced VFs of similar size and variability.Translational relevanceOur study indicates that SKP provides a viable alternative to traditional Goldmann perimetry in clinical trials or care involving both children and adults with IRDs

Standing Balance and Spatiotemporal Aspects of Gait Are Impaired Upon Nocturnal Awakening in Healthy Late Middle-Aged and Older Adults

Study Objectives: Nocturnal awakenings may constitute a unique risk for falls among older adults. We describe differences in gait and balance between presleep and midsleep testing, and whether changes in the lighting environment during the midsleep testing further affect gait and balance. Methods: Twenty-one healthy, late middle-aged and older (64.7 ± 8.0 y) adults participated in this repeated-measures design consisting of four overnight laboratory stays. Each night, participants completed baseline visual acuity, gait, and balance testing. After a 2-h sleep opportunity, they were awakened for 13 min into one of four lighting conditions: very dim white light (\u3c 0.5 lux); dim white light (∼28.0 lux); dim orange light (∼28.0 lux); and white room-level light (∼200 lux). During this awakening, participants completed the same sequence of testing as at baseline. Results: Low-contrast visual acuity significantly decreased with decreasing illuminance conditions (F(3,45) = 98.26, p \u3c 0.001). Our a priori hypothesis was confirmed in that variation in stride velocity and center of pressure path length were significantly worse during the mid-sleep awakening compared to presleep baseline. Lighting conditions during the awakening, however, did not influence these parameters. In exploratory analyses, we found that over one-third of the tested gait and balance parameters were significantly worse at the midsleep awakening as compared to baseline (p \u3c 0.05), and nearly one-quarter had medium to large effect sizes (Cohen d ≥ 0.5; r ≥ 0.3). Conclusions: Balance and gait are impaired during midsleep awakenings among healthy, late middle-aged and older adults. This impairment is not ameliorated by exposure to room lighting, when compared to dim lights

‘The hot-house of decadent chronicle’: Michael Field and the dance of modern verse-drama

This article examines Michael Field's avant-guard poetic dramas post 1895, in particular the Roman Trilogy (The World at Auction, The Race of Leaves, and Julia Domna), to suggest they should be read for their extraordinary poetic experimentation, which precedes, prefigures and is at the heart of modernism's innovations in the genre. It argues that influenced by the works of Friedrich Nietzsche, particularly The Birth of Tragedy, Michael Field turned to Latin decadence and to contemporary German philology to re-energise the genre. The essay also suggests that the Trilogy's emphasis on dance foreshadows the impact of Ballet Russes on modern aesthetics

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Incomplete Cortical Reorganization in Macular Degeneration

This fMRI study shows that there is cortical reorganization of the early visual cortex in both age-related and juvenile-onset macular degeneration, but it is incomplete and task dependent

Reliability of Semiautomated Kinetic Perimetry (SKP) and Goldmann Kinetic Perimetry in Children and Adults With Retinal Dystrophies.

PurposeTo investigate the precision of visual fields (VFs) from semiautomated kinetic perimetry (SKP) on Octopus 900 perimeters, for children and adults with inherited retinal degenerations (IRDs). Goldmann manual kinetic perimetry has long been used in the diagnosis and follow-up of these patients, but SKP is becoming increasingly common. Octopus VFs (OVFs) and Goldmann VFs (GVFs) were both mapped on two occasions.MethodsNineteen females and 10 males with IRDs were tested on OVFs and GVFs, with two targets per test (V4e and one smaller target). Tests were performed in the same (randomized) order at two visits about 1 week apart. The VFs were digitized to derive isopter solid angles. Comparisons, within and between visits, were performed with paired t-tests and Bland-Altman plots.ResultsMedian age was 20 years (range, 7-70; 10 participants aged ≤17 years old). There were no significant differences in solid angles between OVFs and GVFs (P ≥ 0.06) or between the two visits' solid angles on either perimeter (P ≥ 0.30). Between-visit test-retest variability for GVFs and OVFs was similar (P ≥ 0.73), with median values of approximately 9% to 13%. Overall variability was lower for children than adults (medians of 7.5% and 12.8%, respectively).ConclusionsOctopus SKP and Goldmann perimetry produced VFs of similar size and variability.Translational relevanceOur study indicates that SKP provides a viable alternative to traditional Goldmann perimetry in clinical trials or care involving both children and adults with IRDs

Standing Balance and Spatiotemporal Aspects of Gait Are Impaired Upon Nocturnal Awakening in Healthy Late Middle-Aged and Older Adults

10.5664/jcsm.6270JOURNAL OF CLINICAL SLEEP MEDICINE12111477-148

Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial

Background Leber congenital amaurosis, caused by mutations in RPE65 and LRAT, is a severe form of inherited retinal degeneration leading to blindness. We aimed to assess replacement of the missing chromophore 11-cis retinal with oral QLT091001 (synthetic 9-cis-retinyl acetate) in these patients.Methods in our open-label, prospective, phase 1b trial, we enrolled patients (aged >= 6 years) with Leber congenital amaurosis and RPE65 or LRAT mutations at McGill University's Montreal Children's Hospital. Patients received 7 days of oral QLT091001 (10-40 mg/m(2) per day). We assessed patients at baseline and days 7, 9, 14, and 30, and then 2 months and every 2 months thereafter for up to 2.2 years for safety outcomes and visual function endpoints including Goldmann visual fields (GVF), visual acuity, and functional MRI assessment. We regarded patients as having an improvement in vision if we noted at least a 20% improvement in retinal area on GVF compared with baseline or a visual acuity improvement of five or more letters compared with baseline in two consecutive study visits (or any improvement from no vision at baseline). This study is registered with ClinicalTrials.gov, numberNCT01014052.Findings Between December, 2009, and June, 2011, we enrolled and treated 14 patients aged 6-38 years who were followed up until March, 2012. Ten (71%) of 14 patients had an improvement in GVF areas (mean increase in retinal area of 28-683%). Six (43%) patients had an improvement in visual acuity (mean increase of 2-30 letters). Self-reported or parent-reported improvements in activities of daily living supported these findings. After 2 years, 11 (79%) patients had returned to their baseline GVF retinal area and ten (71%) had returned to baseline visual acuity letter values. Thus, three (21%) patients had a sustained GVF response and four (30%) had a sustained visual acuity response. Four patients had functional MRI scans, which correlated with visual response or absence of response to treatment. No serious adverse events occurred, although we noted transient headaches (11 patients), photophobia (11 patients), reduction in serum HDL concentrations (four patients), and increases in serum triglycerides (eight patients) and aspartate aminotransferase concentrations (two patients).Interpretation Non-invasive oral QLT091001 therapy is well tolerated, and can rapidly improve visual function in some patients with Leber congenital amaurosis and RPE65 and LRAT mutations.QLTFoundation Fighting Blindness CanadaCIHRFRSQReseau VisionMcGill Univ, Ctr Hlth, McGill Ocular Genet Lab, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Paediat Surg, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Human Genet, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Montreal Childrens Hosp, Ctr Hlth, Dept Ophthalmol, Montreal, PQ H3H 1P3, CanadaBeijing Union Med Coll Hosp, Beijing, Peoples R ChinaUniversidade Federal de São Paulo, São Paulo, BrazilRotterdam Eye Hosp, Rotterdam, NetherlandsRadboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, NetherlandsRadboud Univ Nijmegen, Med Ctr, Radboud Inst Mol Life Sci, NL-6525 ED Nijmegen, NetherlandsMcGill Univ, Ctr Hlth, McGill Vis Res Unit, Montreal, PQ H3H 1P3, CanadaMcGill Univ, Ctr Hlth, Dept Ophthalmol, Montreal, PQ H3H 1P3, CanadaJohns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USAStanford Univ, Stanford, CA 94305 USAVitreoretinal Associates Washington, Seattle, WA USAUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc