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A letter to the editor is presented in response to an article discussing surveillance scanning of children with medulloblastoma in the March 31, 1994 issue.

Objectives: The clinical impact of rapid sample-to-answer "syndromic" multiplex polymerase chain reaction (PCR) testing for respiratory viruses is not clearly established. We performed a systematic literature review and meta-analysis to evaluate this impact for patients with possible acute respiratory tract infection in the hospital setting., Methods: We searched EMBASE, MEDLINE, and Cochrane databases from 2012 to present and conference proceedings from 2021 for studies comparing clinical impact outcomes between multiplex PCR testing and standard testing., Results: Twenty-seven studies with 17,321 patient encounters were included in this review. Rapid multiplex PCR testing was associated with a reduction of - 24.22 h (95% CI -28.70 to -19.74 h) in the time to results. Hospital length of stay was decreased by -0.82 days (95% CI -1.52 to -0.11 days). Among influenza positive patients, antivirals were more likely to be given (RR 1.25, 95% CI 1.06-1.48) and appropriate infection control facility use was more common with rapid multiplex PCR testing (RR 1.55, 95% CI 1.16-2.07)., Conclusions: Our systematic review and meta-analysis demonstrates a reduction in time to results and length of stay for patients overall along with improvements in appropriate antiviral and infection control management among influenza-positive patients. This evidence supports the routine use of rapid sample-to-answer multiplex PCR testing for respiratory viruses in the hospital setting., Competing Interests: Declaration of Competing Interest TWC has received speaker fees, honoraria, consultancy fees, travel reimbursement, and equipment and consumables free of charge for the purposes of research outside of this submitted study, from BioFire diagnostics and BioMerieux. He has received speaker fees and discounted equipment and consumables from QIAGEN. He has received consultancy fees from, Shionogi, Synairgen research, Roche and Janssen. He has been a member of advisory boards for Roche, Janssen, Cepheid, Shionogi, Sanofi and Seqirus. He is a member of an independent data monitoring committees for a trial sponsored by Roche. He has acted as the UK chief investigator for a trial sponsored by Janssen. TBW, RBH, and TTT are employees of bioMerieux, the sponsor of this study. KL, AB, and JU are employees of IQVIA, which received funding from bioMerieux to conduct this study., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Arginase 1 Deficiency (ARG1-D) is a rare, progressive, metabolic disorder that is characterized by devastating manifestations driven by elevated plasma arginine levels. It typically presents in early childhood with spasticity (predominately affecting the lower limbs), mobility impairment, seizures, developmental delay, and intellectual disability. This systematic review aims to identify and describe the published evidence outlining the epidemiology, diagnosis methods, measures of disease progression, clinical management, and outcomes for ARG1-D patients., Methods: A comprehensive literature search across multiple databases such as MEDLINE, Embase, and a review of clinical studies in ClinicalTrials.gov (with results reported) was carried out per PRISMA guidelines on 20 April 2020 with no date restriction. Pre-defined eligibility criteria were used to identify studies with data specific to patients with ARG1-D. Two independent reviewers screened records and extracted data from included studies. Quality was assessed using the modified Newcastle-Ottawa Scale for non-comparative studies., Results: Overall, 55 records reporting 40 completed studies and 3 ongoing studies were included. Ten studies reported the prevalence of ARG1-D in the general population, with a median of 1 in 1,000,000. Frequently reported diagnostic methods included genetic testing, plasma arginine levels, and red blood cell arginase activity. However, routine newborn screening is not universally available, and lack of disease awareness may prevent early diagnosis or lead to misdiagnosis, as the disease has overlapping symptomology with other diseases, such as cerebral palsy. Common manifestations reported at time of diagnosis and assessed for disease progression included spasticity (predominately affecting the lower limbs), mobility impairment, developmental delay, intellectual disability, and seizures. Severe dietary protein restriction, essential amino acid supplementation, and nitrogen scavenger administration were the most commonly reported treatments among patients with ARG1-D. Only a few studies reported meaningful clinical outcomes of these interventions on intellectual disability, motor function and adaptive behavior assessment, hospitalization, or death. The overall quality of included studies was assessed as good according to the Newcastle-Ottawa Scale., Conclusions: Although ARG1-D is a rare disease, published evidence demonstrates a high burden of disease for patients. The current standard of care is ineffective at preventing disease progression. There remains a clear need for new treatment options as well as improved access to diagnostics and disease awareness to detect and initiate treatment before the onset of clinical manifestations to potentially enable more normal development, improve symptomatology, or prevent disease progression., Competing Interests: Declaration of Competing Interest This study was sponsored by Aeglea BioTherapeutics. Aseel Bin Sawad, John Jackimiec, Mark Bechter, and Allison Trucillo are employees of Aeglea BioTherapeutics. Kristina Lindsley, Anil Bhagat, and Jennifer Uyei are employees of IQVIA. George A. Diaz is employed at the Division of Medical Genetics and Genomics in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and has served as an advisor/consultant and clinical trial investigator for Aeglea BioTherapeutics., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the association between clinical trial registration and risk of bias in clinical trials that have been included in systematic reviews. As a secondary objective, we evaluated the risk of bias among trials registered prospectively vs. retrospectively., Method: Clinical trials published in 2005 or after included in a sample of 100 Cochrane systematic reviews published from 2014-2019., Results: Of 1,177 clinical trials identified, we verified 368 (31%) had been registered, of which 135 (36.7%) were registered prospectively (i.e., before or up to 1 month after enrollment of the first participant). Across the bias domains (one bias assessment for each domain per trial), the percentage of trials at low risk ranged from 29% to 58%; unclear risk ranged from to 26% to 61% and high risk ranged from 2% to 38%. Trials that had been registered had less high or unclear risk of bias in five domains: random sequence generation (univariate risk ratio [RR] 0.69, 95% confidence interval [95% CI] 0.58-0.81), allocation concealment (RR 0.64, 95% CI 0.57-0.72), performance bias (RR 0.65, 95% CI 0.58-0.72), detection bias (RR 0.70, 95% CI 0.62-0.78), and reporting bias (RR 0.62, 95% CI 0.53-0.73). An association between clinical trial registration and high or unclear risk of attrition bias could not be demonstrated nor refuted (RR 1.02, 95% CI 0.89-1.17). It also was observed in terms of overall risk of bias, that registered trials had less high or unclear overall risk of bias than trials that had not been registered (univariate RR 0.29, 95% CI 0.19-0.46). Prospective clinical trial registration was associated with low risks of selection bias due to inadequate allocation concealment, performance bias, and detection bias compared with retrospective clinical trial registration., Conclusion: In a large sample of clinical trials included in recently published systematic reviews of interventions, clinical trial registration was associated with low risk of bias for five of the six domains examined., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Arginase 1 deficiency (ARG1-D) is a rare, progressive and debilitating urea cycle disorder characterized by clinical manifestations including spasticity, seizures, developmental delay, and intellectual disability. The aim of this systematic review was to identify and summarize the natural history of ARG1-D and the unmet needs of patients., Methods: A comprehensive search of published case reports was undertaken to identify patients with ARG1-D regardless of interventions, comparisons, or outcomes. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other evidence-based medicine literature databases were searched on 20 April 2020. Quality was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist. (PROSPERO registration: CRD42020212142.)., Results: One hundred and fifty seven ARG1-D patients were included from 111 publications (good overall quality based on JBI's Checklist); 84 (53.5%) were males. Motor deficits (including spasticity), intellectual disability, and seizures were reported in >50% of the cases. Mean age (SD) at diagnosis was 6.4 years and the laboratory findings most commonly reported to support diagnosis included elevated plasma arginine (81.5%), mutation in ARG1 gene through genetic testing (60%), and absence/reduction of red blood cell arginase activity (51%). Reported management approaches mainly included dietary protein restriction (68%), nitrogen scavengers (45%), and essential amino acid supplements (21%). Author-reported clinical improvement was documented for 26% of patients, 15% deteriorated, and 19% had limited or no change; notably, no indication of clinical outcome was reported for 40% cases., Conclusion: This review illustrates a significant burden of disease and highlights a considerable unmet need for clinically effective treatment options for patients with ARG1-D., Competing Interests: Aseel Bin Sawad is an employee of Aeglea BioTherapeutics. Arti Pothukuchy is an employee of Aeglea BioTherapeutics. Mark Badeaux is an employee of Aeglea BioTherapeutics. Victoria Hodson is an employee of Aeglea BioTherapeutics. Gillian Bubb is an employee of Aeglea BioTherapeutics. Kristina Lindsley is an employee of IQVIA, which provides consulting and other research services to biopharmaceutical companies and received funding from Aeglea BioTherapeutics to conduct this study. Jennifer Uyei is an employee of IQVIA, which provides consulting and other research services to biopharmaceutical companies and received funding from Aeglea BioTherapeutics to conduct this study. George A. Diaz works at the Division of Medical Genetics and Genomics in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and is an external consultant with Aeglea BioTherapeutics., (© 2022 The Authors. JIMD Reports published by John Wiley & Sons Ltd on behalf of SSIEM.)

Objectives: Dipstick tests are frequently used as bedside proteinuria tests to evaluate women suspected of preeclampsia and may inform diagnosis in low resource settings lacking laboratory facilities. This systematic review and meta-analysis aimed to (1) estimate the diagnostic accuracy of urine dipsticks in diagnosing proteinuria, (2) compare performance of different dipstick types and (3) estimate their related costs., Methods: MEDLINE and EMBASE were searched up to August 1, 2020 for primary studies with cross-sectional diagnostic accuracy data on dipstick test(s) compared to a laboratory reference standard (24-hour protein ≥ 300 mg or protein-creatinine ratio ≥ 30 mg/mmol) in pregnant women ≥ 20 weeks of gestation suspected of preeclampsia. Risk of bias and applicability was assessed with QUADAS-2. Data were analysed using a bivariate model with hierarchical addition of covariates for subgroups., Results: Nineteen studies were included. Protein-only dipsticks at 1 + threshold had a pooled sensitivity of 0.68 [95%CI: 0.57-0.77] and specificity of 0.85 [95% CI: 0.73-0.93] (n = 3700 urine samples, 18 studies). Higher specificity was found with automatedly (0.93 [95% CI: 0.82-0.98]) compared to visually (0.81 [95% CI: 0.65-0.91]) read dipsticks, whereas sensitivity was similar and costs were higher. The use of albumin-creatinine ratio (ACR) dipsticks was only reported in two studies and did not improve accuracy. Heterogeneity in study design and prevalence of preeclampsia amongst studies complicated interpretation of pooled estimates., Conclusion: Urine dipsticks performed poorly at excluding preeclampsia in hypertensive pregnant women. Further development of accurate and low-cost bedside proteinuria tests is warranted., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: The objective of the study was to examine whether clinical trials that have been included in systematic reviews have been registered in clinical trial registers and, when they have, whether results of the trials were included in the clinical trial register., Study Design and Setting: This study used a sample of 100 systematic reviews published by the Cochrane Musculoskeletal, Oral, Skin and Sensory Network between 2014 and 2019., Results: We identified 2,000 trials (369,778 participants) from a sample of 100 systematic reviews. The median year of trial publication was 2007. Of 1,177 trials published in 2005 or later, a clinical trial registration record was identified for 368 (31%). Of these registered trials, 135 (37%) were registered prospectively and results were posted for 114 (31%); most registered trials evaluated pharmaceutical interventions (62%). Of trials published in the last 10 years, the proportion of registered trials increased to 38% (261 of 682)., Conclusion: Although some improvement in clinical trial registration has been observed in recent years, the proportion of registered clinical trials included in recently published systematic reviews remains less than desirable. Prospective clinical trial registration provides an essential role in assessing the risk of bias and judging the quality of evidence in systematic reviews of intervention safety and effectiveness., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Disparities in cardiovascular disease (CVD) and associated health and healthcare delivery outcomes have been partially attributed to differential risk factors, and to prevention and treatment inequities within racial and ethnic (including language) minority groups and low socioeconomic status (SES) populations in urban and rural settings. Digital health interventions (DHIs) show promise in promoting equitable access to high-quality care, optimal utilization, and improved outcomes; however, their potential role and impact has not been fully explored. The role of DHIs to mitigate drivers of the health disparities listed above in populations disproportionately affected by atherosclerotic-related CVD was systematically reviewed using published literature (January 2008-July 2020) from multiple databases. Study design, type and description of the technology, health disparities information, type of CVD, outcomes, and notable barriers and innovations associated with the technology utilized were abstracted. Study quality was assessed using the Oxford Levels of Evidence. Included studies described digital health technologies in a disparity population with CVD and reported outcomes. DHIs significantly improved health (eg, clinical, intermediate, and patient-reported) and healthcare delivery (eg, access, quality, and utilization of care) outcomes in populations disproportionately affected by CVD in 24 of 38 included studies identified from 2104 citations. Hypertension control was the most frequently improved clinical outcome. Telemedicine, mobile health, and clinical decision support systems were the most common types of DHIs identified. DHIs improved CVD-related health and healthcare delivery outcomes in racial/ethnic groups and low SES populations in both rural and urban geographies globally., (© 2020 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Evidence-based healthcare (EBHC) principles are essential knowledge for patient and consumer ("consumer") engagement as research and research implementation stakeholders. The aim of this study was to assess whether participation in a free, self-paced online course affects confidence in explaining EBHC topics. The course comprises six modules and evaluations which together take about 6 h to complete., Methods: Consumers United for Evidence-based Healthcare (CUE) designed, tested and implemented a free, online course for consumers, Understanding Evidence-based Healthcare: A Foundation for Action ("Understanding EBHC"). The course is offered through the Johns Hopkins Bloomberg School of Public Health. Participants rated their confidence in explaining EBHC topics on a scale of 1 (lowest) to 5 (highest), using an online evaluation provided before accessing the course ("Before") and after ("After") completing all six course modules. We analyzed data from those who registered for the course from May 31, 2007 to December 31, 2018 (n = 15,606), and among those persons, the 11,522 who completed the "Before" evaluation and 4899 who completed the "After" evaluation. Our primary outcome was the overall mean of within-person change ("overall mean change") in self-reported confidence levels on EBHC-related topics between "Before" and "After" evaluations among course completers. Our secondary outcomes were the mean within-person change for each of the 11 topics (mean change by topic)., Results: From May 31, 2007 to December 31, 2018, 15,606 individuals registered for the course: 11,522 completed the "Before" evaluation, and 4899 of these completed the "After" evaluation (i.e., completed the course). The overall mean change in self-reported confidence levels (ranging from 1 to 5) from the "Before" to "After" evaluation was 1.27 (95% CI, 1.24-1.30). The mean change by topic ranged from 1.00 (95% CI, 0.96-1.03) to 1.90 (95% CI, 1.87-1.94)., Conclusion: Those who seek to involve consumer stakeholders can offer Understanding EBHC as a step toward meaningful consumer engagement. Future research should focus on long-term impact assessment of online course such as ours to understand whether confidence is retained post-course and applied appropriately.

Background: Keratoconus is a degenerative condition of the cornea that profoundly affects vision and vision-specific quality of life. The axial cornea thins and protrudes, resulting in irregularity and, eventually, scarring of the cornea. There are multiple options available for treating keratoconus. Intrastromal corneal ring segments are small, crescent-shaped plastic rings that are placed in the deep, peripheral corneal stroma in order to flatten the cornea. They are made of polymethylmethacrylate (PMMA). The procedure does not involve corneal tissue nor does it invade the central optical zone. Intrastromal corneal ring segments are approved for use when contact lenses or spectacles are no longer adequate., Objectives: To evaluate the effectiveness and safety of intrastromal corneal ring segments as a treatment for keratoconus., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 1); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not implement any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 25 January 2018., Selection Criteria: Two review authors independently assessed records from the electronic searches to identify randomized controlled trials (RCTs). Disagreements were resolved by discussion., Data Collection and Analysis: We planned for two authors to independently review full-text reports, using standard methodological procedures expected by Cochrane., Main Results: We found no RCTs comparing intrastromal corneal ring segments with spectacles or contact lenses., Authors' Conclusions: In the absence of eligible RCTs to review, no conclusions can be drawn.

Background: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to AMD accounts for most cases of AMD-related severe vision loss. Intravitreous injection of anti-vascular endothelial growth factor (anti-VEGF) agents aims to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, to improve vision., Objectives: • To investigate ocular and systemic effects of, and quality of life associated with, intravitreous injection of three anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) versus no anti-VEGF treatment for patients with neovascular AMD• To compare the relative effects of one of these anti-VEGF agents versus another when administered in comparable dosages and regimens SEARCH METHODS: To identify eligible studies for this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (searched January 31, 2018); MEDLINE Ovid (1946 to January 31, 2018); Embase Ovid (1947 to January 31, 2018); the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 31, 2018); the International Standard Randomized Controlled Trials Number (ISRCTN) Registry (www.isrctn.com/editAdvancedSearch - searched January 31, 2018); ClinicalTrials.gov (www.clinicaltrials.gov - searched November 28, 2018); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en - searched January 31, 2018). We did not impose any date or language restrictions in electronic searches for trials., Selection Criteria: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or versus a control treatment (e.g. sham treatment, photodynamic therapy), in which participants were followed for at least one year., Data Collection and Analysis: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We compared outcomes using risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by Cochrane., Main Results: We included 16 RCTs that had enrolled a total of 6347 participants with neovascular AMD (the number of participants per trial ranged from 23 to 1208) and identified one potentially relevant ongoing trial. Six trials compared anti-VEGF treatment (pegaptanib, ranibizumab, or bevacizumab) versus control, and 10 trials compared bevacizumab versus ranibizumab. Pharmaceutical companies conducted or sponsored four trials but funded none of the studies that evaluated bevacizumab. Researchers conducted these trials at various centers across five continents (North and South America, Europe, Asia, and Australia). The overall certainty of the evidence was moderate to high, and most trials had an overall low risk of bias. All but one trial had been registered prospectively.When compared with those who received control treatment, more participants who received intravitreous injection of any of the three anti-VEGF agents had gained 15 letters or more of visual acuity (risk ratio [RR] 4.19, 95% confidence interval [CI] 2.32 to 7.55; moderate-certainty evidence), had lost fewer than 15 letters of visual acuity (RR 1.40, 95% CI 1.27 to 1.55; high-certainty evidence), and showed mean improvement in visual acuity (mean difference 6.7 letters, 95% CI 4.4 to 9.0 in one pegaptanib trial; mean difference 17.8 letters, 95% CI 16.0 to 19.7 in three ranibizumab trials; moderate-certainty evidence) after one year of follow-up. Participants treated with anti-VEGF agents showed improvement in morphologic outcomes (e.g. size of CNV, central retinal thickness) compared with participants not treated with anti-VEGF agents (moderate-certainty evidence). No trial directly compared pegaptanib versus another anti-VEGF agent and followed participants for one year; however, when compared with control treatments, ranibizumab and bevacizumab each yielded larger improvements in visual acuity outcomes than pegaptanib.Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same RCTs compared the same regimens with respect to gain of 15 or more letters of visual acuity (RR 0.95, 95% CI 0.81 to 1.12; high-certainty evidence) and loss of fewer than 15 letters of visual acuity (RR 1.00, 95% CI 0.98 to 1.02; high-certainty evidence); results showed similar mean improvement in visual acuity (mean difference [MD] -0.5 letters, 95% CI -1.5 to 0.5; high-certainty evidence) after one year of follow-up, despite the substantially lower cost of bevacizumab compared with ranibizumab. Reduction in central retinal thickness was less among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -11.6 μm, 95% CI -21.6 to -1.7; high-certainty evidence); however, this difference is within the range of measurement error, and we did not interpret it to be clinically meaningful.Ocular inflammation and increased intraocular pressure (IOP) after intravitreal injection were the most frequently reported serious ocular adverse events. Researchers reported endophthalmitis in less than 1% of anti-VEGF-treated participants and in no cases among control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to show a meaningful difference between groups (evidence of low- to moderate-certainty). Investigators rarely measured and reported data on visual function, quality of life, or economic outcomes., Authors' Conclusions: Results of this review show the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; studies show that ranibizumab and bevacizumab improved visual acuity in some eyes that received these agents and were equally effective. Available information on the adverse effects of each medication does not suggest a higher incidence of potentially vision-threatening complications with intravitreous injection of anti-VEGF agents compared with control interventions; however, clinical trial sample sizes were not sufficient to estimate differences in rare safety outcomes. Future Cochrane Reviews should incorporate research evaluating variable dosing regimens of anti-VEGF agents, effects of long-term use, use of combination therapies (e.g. anti-VEGF treatment plus photodynamic therapy), and other methods of delivering these agents.

Background: Traumatic hyphema is the entry of blood into the anterior chamber (the space between the cornea and iris) subsequent to a blow or a projectile striking the eye. Hyphema uncommonly causes permanent loss of vision. Associated trauma (e.g. corneal staining, traumatic cataract, angle recession glaucoma, optic atrophy, etc.) may seriously affect vision. Such complications can lead to permanent impairment of vision. People with sickle cell trait/disease may be particularly susceptible to increases of elevated intraocular pressure. If rebleeding occurs, the rates and severity of complications increase., Objectives: To assess the effectiveness of various medical interventions in the management of traumatic hyphema., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase.com; PubMed (1948 to June 2018); the ISRCTN registry; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the search was 28 June 2018., Selection Criteria: Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. In this review, we included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical intervention or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions regarding age, gender, severity of the closed-globe trauma, or level of visual acuity at the time of enrollment., Data Collection and Analysis: Two review authors independently extracted the data for the primary outcomes, visual acuity and time to resolution of primary hemorrhage, and secondary outcomes including: secondary hemorrhage and time to rebleed; risk of corneal blood staining, glaucoma or elevated intraocular pressure, optic atrophy, or peripheral anterior synechiae; adverse events; and duration of hospitalization. We entered and analyzed data using Review Manager 5. We performed meta-analyses using a fixed-effect model and reported dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD)., Main Results: We included 20 randomized and seven quasi-randomized studies with a total of 2643 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest.We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Eight trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty.Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60) as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two studies with 121 participants. We assessed the certainty of these findings as low and very low, respectively. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.31, 95% CI 0.17 to 0.55) in five trials with 578 participants, as did aminomethylbenzoic acid as reported in one study (RR 0.10, 95% CI 0.02 to 0.41). The evidence to support an associated reduction in the risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect in the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention.The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials.We found no evidence of an effect between a single versus binocular patch or ambulation versus complete bed rest on the risk of secondary hemorrhage or time to rebleed., Authors' Conclusions: We found no evidence of an effect on visual acuity by any of the interventions evaluated in this review. Although evidence was limited, it appears that people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhaging. However, hyphema took longer clear in people treated with systemic aminocaproic acid.There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema other than possibly to reduce the rate of secondary hemorrhage. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as binocular patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.

Background: Cataract surgery is practiced widely, and substantial resources are committed to an increasing cataract surgical rate in low- and middle-income countries. With the current volume of cataract surgery and future increases, it is critical to optimize the safety and cost-effectiveness of this procedure. Most cataracts are performed on older individuals with correspondingly high systemic and ocular comorbidities. It is likely that routine preoperative medical testing will detect medical conditions, but it is questionable whether these conditions should preclude individuals from cataract surgery or change their perioperative management., Objectives: 1. To investigate the evidence for reductions in adverse events through preoperative medical testing2. To estimate the average cost of performing routine medical testing SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); Ovid MEDLINE; Embase.com; PubMed; LILACS BIREME, the metaRegister of Controlled Trials (mRCT) (last searched 5 January 2012); ClinicalTrials.gov and the WHO ICTRP. The date of the search was 29 June 2018, with the exception of mRCT which is no longer in service. We searched the references of reports from included studies for additional relevant studies without restrictions regarding language or date of publication., Selection Criteria: We included randomized clinical trials in which routine preoperative medical testing was compared to no preoperative or selective preoperative testing prior to age-related cataract surgery., Data Collection and Analysis: Two review authors independently assessed abstracts to identify possible trials for inclusion. For each included study, two review authors independently documented study characteristics, extracted data, and assessed risk of bias., Main Results: We identified three randomized clinical trials that compared routine preoperative medical testing versus selective or no preoperative testing for 21,531 cataract surgeries. The largest trial, in which 19,557 surgeries were randomized, was conducted in Canada and the USA. Another study was conducted in Brazil and the third in Italy. Although the studies had some issues with respect to performance and detection bias due to lack of masking (high risk for one study, unclear for two studies), we assessed the studies as at overall low risk of bias.The three randomized clinical trials included in this review reported results for 21,531 total cataract surgeries with 707 total surgery-associated medical adverse events, including 61 hospitalizations and three deaths. Of the 707 medical adverse events reported, 353 occurred in the pre-testing group and 354 occurred in the no-testing group (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.86 to 1.16; high-certainty evidence). Most events were cardiovascular and occurred during the intraoperative period. Routine preoperative medical testing did not reduce the risk of intraoperative (OR 0.99, 95% CI 0.71 to 1.38) or postoperative ocular adverse events (OR 1.11, 95% CI 0.74 to 1.67) when compared to selective or no testing (2 studies; 2281 cataract surgeries; moderate-certainty evidence). One study evaluated cost savings, estimating the costs to be 2.55 times higher in those with preoperative medical testing compared to those without preoperative medical testing (1 study; 1005 cataract surgeries; moderate-certainty evidence). There was no difference in cancellation of surgery between those with preoperative medical testing and those with selective or no preoperative testing, reported by two studies with 20,582 cataract surgeries (OR 0.97, 95% CI 0.78 to 1.21; high-certainty evidence). No study reported outcomes related to clinical management changes (other than cancellation) or quality of life scores., Authors' Conclusions: This review has shown that routine preoperative testing does not increase the safety of cataract surgery. Alternatives to routine preoperative medical testing have been proposed, including self administered health questionnaires, which could substitute for health provider histories and physical examinations. Such avenues may lead to cost-effective means of identifying those at increased risk of medical adverse events due to cataract surgery. However, despite the rare occurrence, adverse medical events precipitated by cataract surgery remain a concern because of the large number of elderly patients with multiple medical comorbidities who have cataract surgery in various settings. The studies summarized in this review should assist recommendations for the standard of care of cataract surgery, at least in low- and middle-income settings. Unfortunately, in these settings, medical history questionnaires may be useless to screen for risk because few people have ever been to a physician, let alone been diagnosed with any chronic disease.

Purpose: The purpose of this focused review was to explore the etiologies of corneal blindness worldwide and compare them with the indications and type of keratoplasties (eg, full-thickness penetrating keratoplasty, anterior lamellar keratoplasty, or endothelial keratoplasty) performed., Methods: A literature search of the articles published in the top 10 journals (based on the Altmetrics score) relevant to corneal transplantation within the past 20 years was performed to determine how the focus within corneal transplantation has changed over time. These data were compared with the prevalence and etiology of corneal blindness in each respective region worldwide., Results: The leading etiologies of corneal blindness worldwide are primarily due to anterior corneal pathology with a normal endothelium, and the prevalence is highest in developing countries. In addition, the number and type of corneal transplantations performed globally indicate that current practices are disproportionately skewed in favor of endothelial keratoplasty, which is targeted for the pathology prevalent in developed countries. Despite the large number of individuals who would benefit from anterior lamellar keratoplasty, this technique seems to be infrequently performed., Conclusions: Most corneal blindness worldwide is secondary to anterior corneal pathology because of infections and trauma. However, this does not align with the current trends and practices in the field of corneal transplantation. We discuss potential solutions to address the current leading causes of global corneal blindness, including increasing the number of anterior lamellar keratoplasties performed, using long-term preserved corneas by trained surgeons, and improving eye bank handling and distribution of procured tissues.

Importance: Trustworthy clinical practice guidelines require reliable systematic reviews of the evidence to support recommendations. Since 2016, the American Academy of Ophthalmology (AAO) has partnered with Cochrane Eyes and Vision US Satellite to update their guidelines, the Preferred Practice Patterns (PPP)., Objective: To describe experiences and findings related to identifying reliable systematic reviews that support topics likely to be addressed in the 2016 update of the 2011 AAO PPP guidelines on cataract in the adult eye., Design, Setting, and Participants: Cross-sectional study. Systematic reviews on the management of cataract were searched for in an established database. Each relevant systematic review was mapped to 1 or more of the 24 management categories listed under the Management section of the table of contents of the 2011 AAO PPP guidelines. Data were extracted to determine the reliability of each systematic review using prespecified criteria, and the reliable systematic reviews were examined to find whether they were referenced in the 2016 AAO PPP guidelines. For comparison, we assessed whether the reliable systematic reviews published before February 2010 the last search date of the 2011 AAO PPP guidelines were referenced in the 2011 AAO PPP guidelines. Cochrane Eyes and Vision US Satellite did not provide systematic reviews to the AAO during the development of the 2011 AAO PPP guidelines., Main Outcomes and Measures: Systematic review reliability was defined by reporting eligibility criteria, performing a comprehensive literature search, assessing methodologic quality of included studies, using appropriate methods for meta-analysis, and basing conclusions on review findings., Results: From 99 systematic reviews on management of cataract, 46 (46%) were classified as reliable. No evidence that a comprehensive search had been conducted was the most common reason a review was classified as unreliable. All 46 reliable systematic reviews were cited in the 2016 AAO PPP guidelines, and 8 of 15 available reliable reviews (53%) were cited in the 2011 PPP guidelines., Conclusions and Relevance: The partnership between Cochrane Eyes and Vision US Satellite and the AAO provides the AAO access to an evidence base of relevant and reliable systematic reviews, thereby supporting robust and efficient clinical practice guidelines development to improve the quality of eye care.

Background: Glaucoma is a leading cause of blindness worldwide. It results in a progressive loss of peripheral vision and, in late stages, loss of central vision leading to blindness. Early treatment of glaucoma aims to prevent or delay vision loss. Elevated intraocular pressure (IOP) is the main causal modifiable risk factor for glaucoma. Aqueous outflow obstruction is the main cause of IOP elevation, which can be mitigated either by increasing outflow or reducing aqueous humor production. Cyclodestructive procedures use various methods to target and destroy the ciliary body epithelium, the site of aqueous humor production, thereby lowering IOP. The most common approach is laser cyclophotocoagulation., Objectives: To assess the effectiveness and safety of cyclodestructive procedures for the management of non-refractory glaucoma (i.e. glaucoma in an eye that has not undergone incisional glaucoma surgery). We also aimed to compare the effect of different routes of administration, laser delivery instruments, and parameters of cyclophotocoagulation with respect to IOP control, visual acuity, pain control, and adverse events., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 8); Ovid MEDLINE; Embase.com; LILACS; the metaRegister of Controlled Trials (mRCT) and ClinicalTrials.gov. The date of the search was 7 August 2017. We also searched the reference lists of reports from included studies., Selection Criteria: We included randomized controlled trials of participants who had undergone cyclodestruction as a primary treatment for glaucoma. We included only head-to-head trials that had compared cyclophotocoagulation to other procedural interventions, or compared cyclophotocoagulation using different types of lasers, delivery methods, parameters, or a combination of these factors., Data Collection and Analysis: Two review authors independently screened search results, assessed risks of bias, extracted data, and graded the certainty of the evidence in accordance with Cochrane standards., Main Results: We included one trial (92 eyes of 92 participants) that evaluated the efficacy of diode transscleral cyclophotocoagulation (TSCPC) as primary surgical therapy. We identified no other eligible ongoing or completed trial. The included trial compared low-energy versus high-energy TSCPC in eyes with primary open-angle glaucoma. The trial was conducted in Ghana and had a mean follow-up period of 13.2 months post-treatment. In this trial, low-energy TSCPC was defined as 45.0 J delivered, high-energy as 65.5 J delivered; it is worth noting that other trials have defined high- and low-energy TSCPC differently. We assessed this trial to have had low risk of selection bias and reporting bias, unclear risk of performance bias, and high risk of detection bias and attrition bias. Trial authors excluded 13 participants with missing follow-up data; the analyses therefore included 40 (85%) of 47 participants in the low-energy group and 39 (87%) of 45 participants in the high-energy group.Control of IOP, defined as a decrease in IOP by 20% from baseline value, was achieved in 47% of eyes, at similar rates in the low-energy group and the high-energy groups; the small study size creates uncertainty about the significance of the difference, if any, between energy settings (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.64 to 1.65; 79 participants; low-certainty evidence). The difference in effect between energy settings based on mean decrease in IOP, if any exists, also was uncertain (mean difference (MD) -0.50 mmHg, 95% CI -5.79 to 4.79; 79 participants; low-certainty evidence).Decreased vision was defined as the proportion of participants with a decrease of 2 or more lines on the Snellen chart or one or more categories of visual acuity when unable to read the eye chart. Twenty-three percent of eyes had a decrease in vision. The size of any difference between the low-energy group and the high-energy group was uncertain (RR 1.22, 95% CI 0.54 to 2.76; 79 participants; low-certainty evidence). Data were not available for mean visual acuity and proportion of participants with vision change defined as greater than 1 line on the Snellen chart.The difference in the mean number of glaucoma medications used after cyclophotocoagulation was similar when comparing treatment groups (MD 0.10, 95% CI -0.43 to 0.63; 79 participants; moderate-certainty evidence). Twenty percent of eyes were retreated; the estimated effect of energy settings on the need for retreatment was inconclusive (RR 0.76, 95% CI 0.31 to 1.84; 79 participants; low-certainty evidence). No data for visual field, cost effectiveness, or quality-of-life outcomes were reported by the trial investigators.Adverse events were reported for the total study population, rather than by treatment group. The trial authors stated that most participants reported mild to moderate pain after the procedure, and many had transient conjunctival burns (percentages not reported). Severe iritis occurred in two eyes and hyphema occurred in three eyes. No instances of hypotony or phthisis bulbi were reported. The only adverse outcome that was reported by the treatment group was atonic pupil (RR 0.89 in the low-energy group, 95% CI 0.47 to 1.68; 92 participants; low-certainty evidence)., Authors' Conclusions: There is insufficient evidence to evaluate the relative effectiveness and safety of cyclodestructive procedures for the primary procedural management of non-refractory glaucoma. Results from the one included trial did not compare cyclophotocoagulation to other procedural interventions and yielded uncertainty about any difference in outcomes when comparing low-energy versus high-energy diode TSCPC. Overall, the effect of laser treatment on IOP control was modest and the number of eyes experiencing vision loss was limited. More research is needed specific to the management of non-refractory glaucoma.

Purpose: To evaluate the extent to which intraocular pressure and visual field have been reported as outcomes in randomised controlled trials (also referred to as 'trials') of medical treatments for open-angle glaucoma., Methods: We identified published reports of trials in a systematic review of medical interventions for open-angle glaucoma our group conducted. We assessed whether intraocular pressure and visual field were reported as trial outcomes and classified them to be either completely or incompletely reported for meta-analysis. We also collected data on the length of time patients were followed and source of funding for the trial., Results: As of March 2014, we identified 401 trials that had enrolled 76 861 participants. Eighty per cent of 401 trials provided complete information on intraocular pressure and 11% of the 401 trials provided complete information on visual field. Only a minority of trials followed patients for at least 1 year. About half of all reports in our study stated that receiving funding from the industry., Conclusions: Although the vast majority of trials provided sufficient data for meta-analysis of the effect of medical management of open-angle glaucoma on intraocular pressure, relatively few provided data for analysing the effect on visual field. We considered this as missed opportunity because the data were not available for evidence synthesis. Investigators have an obligation to patients and providers to determine the comparative effectiveness of glaucoma interventions in terms of patient-important outcomes and not to waste data that could have been collected in trials., Competing Interests: Competing interests: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)