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Abstract After Mycobacterium tuberculosis (Mtb) infection, many effector T cells traffic to the lungs, but few become activated. Here we use an antigen receptor reporter mouse (Nur77-GFP) to identify recently activated CD4 T cells in the lungs. These Nur77-GFPHI cells contain expanded TCR clonotypes, have elevated expression of co-stimulatory genes such as Tnfrsf4/OX40, and are functionally more protective than Nur77-GFPLO cells. By contrast, Nur77-GFPLO cells express markers of terminal exhaustion and cytotoxicity, and the trafficking receptor S1pr5, associated with vascular localization. A short course of immunotherapy targeting OX40+ cells transiently expands CD4 T cell numbers and shifts their phenotype towards parenchymal protective cells. Moreover, OX40 agonist immunotherapy decreases the lung bacterial burden and extends host survival, offering an additive benefit to antibiotics. CD4 T cells from the cerebrospinal fluid of humans with HIV-associated tuberculous meningitis commonly express surface OX40 protein, while CD8 T cells do not. Our data thus propose OX40 as a marker of recently activated CD4 T cells at the infection site and a potential target for immunotherapy in tuberculosis.

Background/Aim: The COMPlog clinical visual acuity measuring system is being developed for both routine and research use. This study aimed to validate its performance in amblyopic children and both normal and diseased adults against the gold standard ETDRS chart and the E-ETDRS computerised acuity measurement algorithm. Method: Timed test and retest fully interpolated five letters per line logMAR visual acuity measurements were taken for 70 adults and 59 amblyopic children using the ETDRS chart and the COMPlog visual acuity measurement system. 39 of the adults also underwent computerised acuity testing using the E-ETDRS testing algorithm. The tested adults included normals as well as subjects with a range of ocular diseases. The methods of Bland and Altman were employed with test-retest variability (TRV) expressed as 95% confidence limits for agreement. Results: No significant bias was observed between the gold standard ETDRS acuity measurements and those taken with either COMPIog or E-ETDRS. TRVs of ±0.12 logMAR and ± 0.10 logMAR were respectively found for COMPIog measurements in the amblyopic children and adult groups compared with ±0.12 logMAR for the ETDRS chart in both groups. The TRV of the E-ETDRS system was slightly greater at ± 0.16 logMAR. Median testing times for COMPIog and ETDRS were 95 and 85 s and 66 and 56 s respectively in the paediatric and adult groups and 120 s for the E-ETDRS measurements on adults. Discussion: COMPlog measurements agree well with and are similarly reliable to the gold standard ETDRS chart with comparable test times. E-ETDRS algorithm measurements took approximately twice as long. [ABSTRACT FROM AUTHOR]

Patients undergoing cataract surgery may develop an infective endophthalmitis postoperatively which may result in the loss of an eye. This study was carried out to measure aqueous humour levels and to assess patients' tolerance of ceftazidime, a potent antipseudomonal cephalosporin, given subconjunctivally. Eighteen patients received 125 mg ceftazidime subconjunctivally before they underwent routine cataract surgery. A further two patients received 62.5 mg subconjunctivally. The results show good penetration into the aqueous humour well above the minimum inhibitory concentrations (MICs) of possible pathogens. There were no postoperative infections, no local irritation, and no systemic side effects. [ABSTRACT FROM PUBLISHER]

Myogenic transcription factors with a basic helix-loop-helix (bHLH) such as MYOD, myogenin, MRF4, and MYF5 contribute to muscle differentiation and regulation. The MYF5 gene located on chromosome 12 encodes for myogenic factor 5 (MYF5), which has a role in skeletal and extraocular muscle development and rib formation. Variants in MYF5 were found to cause external ophthalmoplegia with rib and vertebral anomalies (EORVA), a rare recessive condition. To date, three homozygous variants in MYF5 have been reported to cause EORVA in six members of four unrelated families. Here, we present a novel homozygous MYF5 frameshift variant, c.596dupA p. (Asn199Lysfs*49), causing premature protein termination and presenting with external ophthalmoplegia, ptosis, and scoliosis in three siblings from a consanguineous family of Pakistani origin. With four MYF5 variants now discovered, genetic testing and paediatric assessment for extra-ocular features should be considered in all cases of congenital ophthalmoplegia.

One-third of students experience a mental health condition associated with decreased academic functioning and increased risk of dropping out. While mental health difficulties are lower among male students, they are twice as likely to die by suicide. Although the importance of gender-sensitive interventions for male students has been emphasized, feasible and effective approaches are unexplored. This investigation conducted three gender-sensitive feasibility interventions for male students to evaluate acceptability, changes to help-seeking and mental health outcomes. Three interventions were delivered to 24 male students. The interventions included the following: Intervention 1-a formal intervention targeting male students, Intervention 2-a formal intervention that adopted gender-sensitive language and promoted positive masculine traits, and Intervention 3-an informal drop-in offering a social space providing health information. These were evaluated for acceptability, attitudes to help-seeking, and mental health outcomes. All interventions were equally acceptable. The informal drop-in was more acceptable, having better engagement from male students who have greater conformity to maladaptive masculine traits, more negative attitudes to help-seeking, higher levels of self-stigma, who were less likely to have used mental health support before and belonged to an ethnic minority. These findings indicate differences in acceptability, particularly uptake, for hard-to-engage male students. Informal strategies help reach male students who would otherwise not engage with mental health support, familiarize them with help-seeking, and connect them with pre-existing mental health interventions. More work needs to be carried out using larger samples to investigate the efficacy of informal interventions to engage male students.

Background: Current treatments for amblyopia, typically patching or pharmacological blurring, have limited success. Less than two-thirds of children achieve good acuity of 0.20 logMAR in the amblyopic eye, with limited improvement of stereopsis, and poor adherence to treatment. A new approach, based on presentation of movies or computer games separately to each eye, may yield better results and improve adherence. These treatments aim to balance the input of visual information from each eye to the brain.  OBJECTIVES: To determine whether binocular treatments in children, aged three to eight years, with unilateral amblyopia result in better visual outcomes than conventional patching or pharmacological blurring treatment., Search Methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register), MEDLINE, Embase, ISRCTN, ClinicalTrials.gov, and the WHO ICTRP to 19 November 2020, with no language restrictions., Selection Criteria: Two review authors independently screened the results of the search for relevant studies. We included randomised controlled trials (RCTs) that enrolled children between the ages of three and eight years old with unilateral amblyopia. Amblyopia was classed as present when the best-corrected visual acuity (BCVA) was worse than 0.200 logMAR in the amblyopic eye, with BCVA 0.200 logMAR or better in the fellow eye, in the presence of an amblyogenic risk factor, such as anisometropia, strabismus, or both. To be eligible, children needed to have undergone cycloplegic refraction and  ophthalmic examination, including fundal examination and optical treatment, if indicated, with stable BCVA in the amblyopic eye despite good adherence with wearing glasses. We included any type of binocular viewing intervention, on any device (e.g. computer monitors viewed with liquid-crystal display shutter glasses; hand-held screens, including mobile phones with lenticular prism overlay; or virtual reality displays). Control groups received standard amblyopia treatment, which could include patching or pharmacological blurring of the better-seeing eye. We included full-time (all waking hours) and part-time (between 1 and 12 hours a day) patching regimens. We excluded children who had received any treatment other than optical treatment; and studies with less than 8-week follow-up., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. The primary outcome of the review was the change from baseline of distance BCVA in the amblyopic eye after 16 (± 2) weeks of treatment, measured in logMAR units on an age-appropriate acuity test., Main Results: We identified one eligible RCT of conventional patching treatment versus novel binocular treatment, and analysed a subset of 68 children who fulfilled the age criterion of this review. We obtained data for the mean change in amblyopic eye visual acuity, adverse events (diplopia), and adherence to prescribed treatment at 8- and 16-week follow-up intervals, though no data were available for change in BCVA after 52 weeks. Risk of bias for the included study was considered to be low. The certainty of evidence for the visual acuity outcomes at 8 and 16 weeks of treatment and adherence to the study intervention was rated moderate using the GRADE criteria, downgrading by one level due to imprecision. The certainty of evidence was downgraded by two levels and rated low for the proportion of participants reporting adverse events due to the sample size.  Acuity improved in the amblyopic eye in both the binocular and patching groups following 16 weeks of treatment (improvement of -0.21 logMAR in the binocular group and -0.24 logMAR in the patching group, mean difference (MD) 0.03 logMAR (95% confidence interval (CI) -0.10 to 0.04; 63 children). This difference was non-significant and the improvements in both the binocular and patching groups are also considered clinically similar. Following 8 weeks of treatment, acuity improved in both the binocular and patching groups (improvement of -0.18 logMAR in the patching group compared to -0.16 logMAR improvement in the binocular-treatment group) (MD 0.02, 95% CI -0.04 to 0.08). Again this difference was statistically non-significant, and the differences observed between the patching and binocular groups are also clinically non-significant. No adverse event of permanent diplopia was reported. Adherence was higher in the patching group (47% of participants in the iPad group achieved over 75% compliance compared with 90% of the patching group).  Data were not available for changes in stereopsis nor for contrast sensitivity following treatment., Authors' Conclusions: Currently, there is only one RCT that offers evidence of the safety and effectiveness of binocular treatment. The authors are moderately confident that after 16 weeks of treatment, the gain in amblyopic eye acuity with binocular treatment is likely comparable to that of conventional patching treatment. However, due to the limited sample size and lack of long term (52 week) follow-up data, it is not yet possible to draw robust conclusions regarding the overall safety and sustained effectiveness of binocular treatment. Further research, using acknowledged methods of visual acuity and stereoacuity assessment with known reproducibility, is required to inform decisions about the implementation of binocular treatments for amblyopia in clinical practice, and should incorporate longer term follow-up to establish the effectiveness of binocular treatment. Randomised controlled trials should also include outcomes reported by users, adherence to prescribed treatment, and recurrence of amblyopia after cessation of treatment., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction and Hypothesis: This narrative review describes the existing epidemiologic literature and identifies gaps regarding pelvic organ prolapse (POP) prevalence, incidence, natural history, and current and future service needs., Materials and Methods: A PubMed search identified relevant citations published in 2000 or later. Pre-specified criteria were used to screen titles, abstracts, and manuscripts, including reference sections. Study findings were summarized to define what is known, identify gaps in current knowledge, and suggest priority areas for future research., Results: The reported prevalence of POP varies widely (1-65%) based on whether its presence is ascertained by symptoms (1-31%), pelvic examination (10-50%), or both (20-65%). Most existing population-based surveys do not include physical examination data. White women from higher income countries are overrepresented in the existing literature. Incidence and natural history data are limited and consist mainly of cohorts that follow women after pregnancy or menopause. Given global increases in aging populations in well-resourced countries, the need for POP treatment is anticipated to increase in the coming decades. In lower and middle income countries (LMICs) where demographic trends are different, there is a dearth of information about anticipated POP service needs., Conclusion: Future POP incidence, prevalence, and natural history studies should include non-white women from LMICs and should combine pelvic examination data with validated patient-reported outcome measures when feasible. Anticipated future service needs differ globally, with a greater demand for POP treatment services in well-resourced settings where aging populations are prevalent., (© 2021. The International Urogynecological Association.)

Transvaginal mesh/grafts have been popularized over the past 20 years in an attempt to improve the longevity of traditional vaginal pelvic organ prolapse (POP) surgery. Several national bodies have concluded that the proposed benefits of mesh/graft implantation are outweighed by the significant increase in surgery complications related to these products. As a consequence mesh products for vaginal POP surgery have been withdrawn from use in many countries. This article is a narrative review of newer mesh and graft products including lightweight polypropylene mesh products, biological grafts, hybrid grafts, and tissue engineered grafts., Competing Interests: Financial disclaimer/Conflict of interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

PAX6 is considered the master regulator of eye development, the majority of variants affecting this gene cause the pan-ocular developmental eye disorder aniridia. Although no genotype-phenotype correlations are clearly established, missense variants affecting the DNA-binding paired domain of PAX6 are usually associated with non-aniridia phenotypes like microphthalmia, coloboma or isolated foveal hypoplasia. In this study, we report two missense heterozygous variants in the paired domain of PAX6 resulting in isolated foveal hypoplasia with nystagmus in two independent families: c.112 C > G; p.(Arg38Gly) and c.214 G > C; p.(Gly72Arg) in exons 5 and 6, respectively. Furthermore, we provide evidence that paternal postzygotic mosaicism is the cause of inheritance, with clinically unaffected fathers and reduced affected allele fraction. This work contributes to increase the phenotypic spectrum caused by PAX6 variants, and to our knowledge, is the first report to describe the presence of postzygotic parental mosaicism causing isolated foveal hypoplasia with nystagmus. These results support the growing evidence that suggest an overestimation of sporadic cases with PAX6 variants, which has strong implications for both genetic counselling and family planning.

Purpose: We evaluated the 3-year safety and efficacy of the BlueWind Medical RENOVA™ iStim system for the treatment of overactive bladder syndrome., Materials and Methods: All patients who previously underwent implantation with the RENOVA system were offered continued participation. The primary long-term study end point was to evaluate the safety profile based on incidence of serious adverse events (system and/or procedure related), which was measured by the impact and frequency of serious adverse events. The secondary end points included clinical improvement compared to baseline and quality of life improvement compared to baseline at 36 months, which was measured by 3-day voiding diary and quality of life questionnaires at certain time points., Results: Of the 34 patients with overactive bladder syndrome who previously underwent implantation with the RENOVA system 20 consented to continuation in this 3-year followup study. Mean patient age was 56.1 years and 80% (16) of the study cohort was female. The overall treatment success rate was 75% at 36 months in the per protocol (16) and the intent to treat (20) analyses. In total, 73% of the patients reported improvement in health related quality of life scores above the minimal important difference of 10 points., Conclusions: This 3-year followup study using the BlueWind RENOVA iStim system for the treatment of overactive bladder syndrome symptoms confirms the long-term good safety profile with no technical failures reported. Lasting treatment efficacy is mirrored by a sustained positive impact on patient quality of life.

The aetiology of bladder pain syndrome/interstitial cystitis is still unknown. Numerous mechanisms have been proposed and treatments targeting various aspects of these are used. This review looks at the existing evidence on bladder instillations and whether they could be used in the treatment of lower urinary tract symptoms as well.

Interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections carry significant burden for those affected. As women enter the menopause, other factors may influence how these conditions manifest. The urinary microbiome has shown that the urine contains extensive numbers of bacteria. There is some evidence to suggest that it is altered depending on the menopausal state of the individual. It is possible that this alteration may go on to influence how the disease course of interstitial cystitis/bladder pain syndrome and recurrent urinary tract infections runs in the post-menopausal group. The review will explore these two conditions and the potential role of the urinary microbiome.

The ideal treatment for overactive bladder is still elusive. In those where medication fails to improve symptoms options include invasive treatments such as botulinum toxin-A, sacral neural stimulation or posterior tibial nerve stimulation. Scientific professional society guidelines advise percutaneous posterior tibial nerve stimulation as a third line treatment option only after multi-disciplinary team review as well as failure of both conservative and pharmacological management. The aim of this article is to review all techniques for tibial nerve stimulation and their efficacy.

Purpose: To develop a comprehensive next-generation sequencing panel assay that screens genes known to cause developmental eye disorders and inherited eye disease and to evaluate its diagnostic yield in a pediatric cohort with malformations of the globe, anterior segment anomalies, childhood glaucoma, or a combination thereof., Design: Evaluation of diagnostic test., Participants: Two hundred seventy-seven children, 0 to 16 years of age, diagnosed with nonsyndromic or syndromic developmental eye defects without a genetic diagnosis., Methods: We developed a new oculome panel using a custom-designed Agilent SureSelect QXT target capture method (Agilent Technologies, Santa Clara, CA) to capture and perform parallel high-throughput sequencing analysis of 429 genes associated with eye disorders. Bidirectional Sanger sequencing confirmed suspected pathogenic variants., Main Outcome Measures: Collated clinical details and oculome molecular genetic results., Results: The oculome design covers 429 known eye disease genes; these are subdivided into 5 overlapping virtual subpanels for anterior segment developmental anomalies including glaucoma (ASDA; 59 genes), microphthalmia-anophthalmia-coloboma (MAC; 86 genes), congenital cataracts and lens-associated conditions (70 genes), retinal dystrophies (RET; 235 genes), and albinism (15 genes), as well as additional genes implicated in optic atrophy and complex strabismus (10 genes). Panel development and testing included analyzing 277 clinical samples and 3 positive control samples using Illumina sequencing platforms; more than 30× read depth was achieved for 99.5% of the targeted 1.77-Mb region. Bioinformatics analysis performed using a pipeline based on Freebayes and ExomeDepth to identify coding sequence and copy number variants, respectively, resulted in a definitive diagnosis in 68 of 277 samples, with variability in diagnostic yield between phenotypic subgroups: MAC, 8.2% (8 of 98 cases solved); ASDA, 24.8% (28 of 113 cases solved); other or syndromic, 37.5% (3 of 8 cases solved); RET, 42.8% (21 of 49 cases solved); and congenital cataracts and lens-associated conditions, 88.9% (8 of 9 cases solved)., Conclusions: The oculome test diagnoses a comprehensive range of genetic conditions affecting the development of the eye, potentially replacing protracted and costly multidisciplinary assessments and allowing for faster targeted management. The oculome enabled molecular diagnosis of a significant number of cases in our sample cohort of varied ocular birth defects., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

In this best practice document, we propose recommendations for the use of LASER for gynecologic and urologic conditions such as vulvovaginal atrophy, urinary incontinence, vulvodynia, and lichen sclerosus based on a thorough literature review. Most of the available studies are limited by their design; for example, they lack a control group, patients are not randomized, follow-up is short term, series are small, LASER is not compared with standard treatments, and most studies are industry sponsored. Because of these limitations, the level of evidence for the use of LASER in the treatment of these conditions remains low and does not allow for definitive recommendations for its use in routine clinical practice. Histological evidence is commonly reported as proof of tissue regeneration after LASER treatment. However, the histological changes noted can also be consistent with reparative changes after a thermal injury rather than necessarily representing regeneration or restoration of function. The use of LASER in women with vulvodynia or lichen sclerosus should not be recommended in routine clinical practice. There is no biological plausibility or safety data on its use on this population of women. The available clinical studies do not present convincing data regarding the efficacy of LASER for the treatment of vaginal atrophy or urinary incontinence. Also, although short-term complications seem to be uncommon, data concerning long-term outcomes are lacking. Therefore, at this point, LASER is not recommended for routine treatment of the aforementioned conditions unless part of well-designed clinical trials or with special arrangements for clinical governance, consent, and audit.

Aims: Energy-based devices using radiofrequency and laser technologies have gained popularity as therapies for vaginal atrophy, urinary incontinence, and vaginal prolapse. They have been promoted by cosmetic and aesthetic industries for vaginal "laxity" and vaginal "rejuvenation," both of which are undefined conditions and terms. This article aims to review the current available literature and its quality on this emerging technology., Methods: An international panel of gynaecologists, urogynaecologists, and urologists undertook a review of the available published literature, identifying articles, guidance, and society statements on the use vaginal energy-based devices., Results: There is currently no formal guidance for the use of vaginal energy based therapies. No randomized controlled trials have been published. No comparative studies to existing treatment has been carried out. Studies suggest that vaginal laser can be used in the treatment of vaginal prolapse or "vaginal laxity" and stress urinary incontinence with no quality evidence supporting the use of the therapy for vaginal atrophy or lichen sclerosis., Conclusions: This international group propose that whilst there remains a paucity of good quality data describing the safety, benefits, and appropriate use of vaginal radiofrequency or laser treatments in gynaecology and urogynaecology, a consensus best practice document by an established scientific community needs to be developed., (© 2019 Wiley Periodicals, Inc.)

Purpose: To determine the child's and parental perception of functional visual ability (FVA), vision-related and health-related quality of life (VR-QoL, HR-QoL) in children with microphthalmia/anophthalmia/coloboma (MAC)., Methods: Between June 25, 2014, and June 3, 2015, we carried out a cross-sectional observational study at Moorfields Eye Hospital, London, UK, enrolling 45 children 2-16 years of age with MAC attending our clinics, and their parents. To assess FVA, VR-QoL, and HR-QoL we asked participants to complete three validated tools, the Cardiff Visual Ability Questionnaire for Children (CVAQC), the Impact of Vision Impairment for Children (IVI-C) instrument, and the PedsQL V 4.0. The main outcome measures were the FVA, VR-QoL, and HR-QoL scores, reported by children and parents., Results: In children with MAC, FVA is moderately reduced, with a median CVAQC score of -1.4 (IQR, -2.4 to 0.4; range, -3.0 [higher FVA] to +2.8 [lower FVA]). VR-QoL and HR-QoL are greatly reduced, with an IVI-C median score of 63 (IQR, 52-66; normal VR-QoL, 96), a median self-reported PedsQL score of 77 (IQR, 71-90; normal HR-QoL, 100) and parental score of 79 (IQR, 61-93), and a family impact score of 81 (67-93). Psychosocial well-being scores are lower than physical well-being scores. Parents and children have a different perception of the impact of the condition on the child's HR-QoL., Conclusions: MAC has a significant impact on a child's FVA and QoL, similar to that described by children with acute lymphoblastic leukaemia and chronic systemic conditions. Children and families may benefit from psychosocial support., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Strabismus (misalignment of the eyes) is a risk factor for impaired visual development both of visual acuity and of stereopsis. Detection of strabismus in the community by non-expert examiners may be performed using a number of different index tests that include direct measures of misalignment (corneal or fundus reflex tests), or indirect measures such as stereopsis and visual acuity. The reference test to detect strabismus by trained professionals is the cover‒uncover test., Objectives: To assess and compare the accuracy of tests, alone or in combination, for detection of strabismus in children aged 1 to 6 years, in a community setting by non-expert screeners or primary care professionals to inform healthcare commissioners setting up childhood screening programmes.Secondary objectives were to investigate sources of heterogeneity of diagnostic accuracy., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library, the Health Technology Assessment Database (HTAD) in the Cochrane Library (2016, Issue 4), MEDLINE Ovid (1946 to 5 January 2017), Embase Ovid (1947 to 5 January 2017), CINAHL (January 1937 to 5 January 2017), Web of Science Conference Proceedings Citation Index-Science (CPCI-S) (January 1990 to 5 January 2017), BIOSIS Previews (January 1969 to 5 January 2017), MEDION (to 18 August 2014), the Aggressive Research Intelligence Facility database (ARIF) (to 5 January 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 5 January 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 5 January 2017 and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 5 January 2017. We did not use any date or language restrictions in the electronic searches for trials. In addition, orthoptic journals and conference proceedings without electronic listings were searched., Selection Criteria: All prospective or retrospective population-based test accuracy studies of consecutive participants were included. Studies compared a single or combination of index tests with the reference test. Only those studies with sufficient data for analysis were included specifically to calculate sensitivity and specificity and determine diagnostic accuracy.Participants were aged 1 to 6 years. Studies reporting participants outside this range were included if subgroup data were available.Permitted settings included population-based vision screening programmes or opportunistic screening programmes, such as those performed in schools., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane. In brief, two review authors independently assessed titles and abstracts for eligibility and extracted the data, with a third senior author resolving any disagreement. We analysed data primarily for specificity and sensitivity., Main Results: One study from a total of 1236 papers, abstracts and trials was eligible for inclusion with a total number of participants of 335 of which 271 completed both the screening test and the gold standard test. The screening test using an automated photoscreener had a sensitivity of 0.46 (95% confidence interval (CI) 0.19 to 0.75) and specificity of 0.97 (CI 0.94 to 0.99). The overall number affected by strabismus was low at 13 (4.8%)., Authors' Conclusions: There is very limited data in the literature to ascertain the accuracy of tests for detecting strabismus in the community as performed by non-expert screeners. A large prospective study to compare methods would be required to determine which tests have the greatest accuracy.

Purpose: To evaluate the effect of glaucoma on functional vision and on vision-related (VR) and health-related (HR) quality of life (QoL) in children up to 16 years of age., Design: Cross-sectional observational study., Participants: One hundred nineteen children 2 to 16 years of age (mean age, 9.4 years; standard deviation [SD], 4.56 years) with glaucoma and their parents., Methods: Completion of 3 validated instruments for children to assess (1) functional visual ability (FVA) with the Cardiff Visual Ability Questionnaire for Children (CVAQC), (2) VR QoL with the Impact of Vision Impairment for Children (IVI-C), and (3) HR QoL with the Pediatric Quality of Life Inventory (PedsQL) version 4.0., Main Outcome Measures: Cardiff Visual Ability Questionnaire for Children, IVI-C, and PedsQL scores., Results: Scores for FVA, VR QoL, and HR QoL were reduced in children with glaucoma: median CVAQC score, -1.24 (interquartile range [IQR], -2.2 to -0.11; range, -3.00 higher visual ability to +2.80 lower visual ability); mean IVI-C score, 67.3 (SD, 14.4; normal VR QoL, 96); median PedsQL self-report, 78.8 (IQR, 67.4-90.2); parent report, 71.2 (IQR, 55.7-85.8); and family impact score, 74.3 (IQR, 56.9-88.5; normal HR QoL, 100). Psychosocial subscores were lower than physical subscores on the PedsQL. Older children reported less impairment on CVAQC, IVI-C, and PedsQL than younger children. Parents reported greater impact on their child's HR QoL than children reported themselves., Conclusions: Glaucoma and its management have a marked impact on a child's FVA and QoL. Children with glaucoma report HR QoL scores similar to those described by children with severe congenital cardiac defects, who have undergone liver transplants, or who have acute lymphoblastic leukemia., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The Peroxiredoxin Q (PrxQ) proteins are thiol-based peroxidases that are important for maintaining redox homeostasis in several organisms. Activity of PrxQs is mediated by two cysteines, peroxidatic (C p ) and resolving (C r ), in association with a reducing partner. A PrxQ, Alr3183, from the cyanobacterium, Anabaena PCC 7120, was characterized in this study. Alr3183, which required thioredoxin A (TrxA) for peroxidase activity, was an intramolecular disulfide bond-containing monomeric protein. However, Alr3183 lacking C p (Alr3183C46S) or C r (Alr3183C51S) formed intermolecular disulfide linkages and was dimeric. Alr3183C46S was completely inactive, while Alr3183C51S required higher concentration of TrxA for peroxidase activity. Surface plasmon resonance analysis showed that unlike Alr3183 or Alr3183C46S, Alr3183C51S bound rather poorly to TrxA. Also, compared to the oxidized protein, the DTT-treated (reduced) Alr3183 displayed decreased interaction with TrxA. In vivo, Alr3183 was found to be induced in response to γ-radiation. On exposure to H 2 O 2 , Anabaena strain over-expressing Alr3183 showed reduced formation of ROS, intact photosynthetic pigments and consequently better survival than the wild-type, whereas overproduction of Alr3183C46S did not provide any protection. Significantly, this study (1) reveals the importance of C r for interaction with thioredoxins and (2) demonstrates that over-expression of PrxQs can protect cyanobacteria from oxidative stresses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To increase the detection rate of strabismus on digital photographs, with the ultimate aim of developing a new automated strabismus detection algorithm., Methods: In this prospective case series, the authors acquired digital face photographs of 409 children with manifest or latent strabismus, using a 14-million-pixel camera with CCD image sensor. Of the last 52 enrolled, 34 image sets were selected for this study: 29 with manifest and 5 with latent strabismus. Images were taken at a distance of 40 to 70 cm in primary position, with the camera lens as the fixation target and in slight off-center fixation, and using a novel target of small light-emitting diodes mounted onto the camera case. The location of the corneal light reflection was manually calculated in relation to the center of the pupil in both eyes and ocular deviation as the difference in corneal light reflection location between the two eyes. In orthotropia, the expected deviation is zero., Results: In children with phorias, the mean corneal light reflection location difference between the eyes was -0.10 ± 0.14 mm in primary position and -2.02 ± 0.39 mm in off-center fixation. Using a threshold of ±0.5 mm on either side of zero for central and of 2 mm for off-center fixation, sensitivity to detect strabismus increased from 65.6% in central to 79.3% in off-center fixation, respectively. The calculation of specificity will require inclusion of a population of individuals without strabismus., Conclusions: Off-center fixation onto a near target ensures that participants are actively looking at the target and may increase accommodative effort, thereby increasing the detection rate of strabismus. [J Pediatr Ophthalmol Strabismus. 2017;54(2):90-96.]., (Copyright 2017, SLACK Incorporated.)

Background/aims: Children and adults with neurological impairments are often not able to access conventional perimetry; however, information about the visual field is valuable. A new technology, saccadic vector optokinetic perimetry (SVOP), may have improved accessibility, but its accuracy has not been evaluated. We aimed to explore accessibility, testability and accuracy of SVOP in children with neurodisability or isolated visual pathway deficits., Methods: Cohort study; recruitment October 2013-May 2014, at children's eye clinics at a tertiary referral centre and a regional Child Development Centre; full orthoptic assessment, SVOP (central 30° of the visual field) and confrontation visual fields (CVF). Group 1: age 1-16 years, neurodisability (n=16), group 2: age 10-16 years, confirmed or suspected visual field defect (n=21); group 2 also completed Goldmann visual field testing (GVFT)., Results: Group 1: testability with a full 40-point test protocol is 12.5%; with reduced test protocols, testability is 100%, but plots may be clinically meaningless. Children (44%) and parents/carers (62.5%) find the test easy. SVOP and CVF agree in 50%. Group 2: testability is 62% for the 40-point protocol, and 90.5% for reduced protocols. Corneal changes in childhood glaucoma interfere with SVOP testing. All children and parents/carers find SVOP easy. Overall agreement with GVFT is 64.7%., Conclusions: While SVOP is highly accessible to children, many cannot complete a full 40-point test. Agreement with current standard tests is moderate to poor. Abnormal saccades cause an apparent non-specific visual field defect. In children with glaucoma or nystagmus SVOP calibration often fails., (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/)

Introduction or Background: With a prevalence of 2-5%, amblyopia is the most common vision deficit in children in the UK and the second most common cause of functional low vision in children in low-income countries., Sources of Data: Pubmed, Cochrane library and clinical trial registries (clinicaltrials.gov, ISRCTN, UKCRN portfolio database)., Areas of Agreement: Screening and treatment at the age of 4-5 years are cost efficient and clinically effective. Optical treatment (glasses) alone can improve visual acuity, with residual amblyopia treated by part-time occlusion or pharmacological blurring of the better-seeing eye. Treatment after the end of the conventional 'critical period' can improve vision, but in strabismic amblyopia carries a low risk of double vision., Areas of Controversy: It is not clear whether earlier vision screening would be cost efficient and associated with better outcomes. Optimization of treatment by individualized patching regimes or early start of occlusion, and novel binocular treatment approaches may enhance adherence to treatment, provide better outcomes and shorten treatment duration., Growing Points: Binocular treatments for amblyopia., Areas Timely for Developing Research: Impact of amblyopia on education and quality of life; optimal screening timing and tests; optimal administration of conventional treatments; development of child-friendly, effective and safe binocular treatments., (© The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Current treatments for amblyopia in children, occlusion and pharmacological blurring, have had limited success, with less than two-thirds of children achieving good visual acuity of at least 0.20 logMAR in the amblyopic eye, limited improvement of stereopsis, and poor compliance. A new treatment approach, based on the dichoptic presentation of movies or computer games (images presented separately to each eye), may yield better results, as it aims to balance the input of visual information from each eye to the brain. Compliance may also improve with these more child-friendly treatment procedures., Objectives: To determine whether binocular treatments in children aged three to eight years with unilateral amblyopia result in better visual outcomes than conventional occlusion or pharmacological blurring treatment., Search Methods: We searched the Cochrane Eyes and Vision Group Trials Register (last date of searches: 14 April 2015), the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to April 2015), EMBASE (January 1980 to April 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials., Selection Criteria: Two review authors independently screened the results of the search in order to identify studies that met the inclusion criteria of the review: randomised controlled trials (RCTs) that enrolled participants between the ages of three and eight years old with unilateral amblyopia, defined as best-corrected visual acuity (BCVA) worse than 0.200 logMAR in the amblyopic eye, and BCVA 0.200 logMAR or better in the fellow eye, in the presence of an amblyogenic risk factor such as anisometropia, strabismus, or both. Prior to enrolment, participants were to have undergone a cycloplegic refraction and comprehensive ophthalmic examination including fundal examination. In addition, participants had to have completed a period of optical treatment, if indicated, and BCVA in the amblyopic eye had to remain unchanged on two consecutive assessments despite reportedly good compliance with glasses wearing. Participants were not to have received any treatment other than optical treatment prior to enrolment. We planned to include any type of binocular viewing intervention; these could be delivered on different devices including computer monitors viewed with LCD shutter glasses or hand-held screens including mobile phone screens with lenticular prism overlay. Control groups were to have received standard amblyopia treatment; this could include occlusion or pharmacological blurring of the better-seeing eye. We planned to include full-time (all waking hours) and part-time (between 1 and 12 hours a day) occlusion regimens., Data Collection and Analysis: We planned to use standard methodological procedures expected by The Cochrane Collaboration. We had planned to meta-analyse the primary outcome, that is mean distance BCVA in the amblyopic eye at 12 months after the cessation of treatment., Main Results: We could identify no RCTs in this subject area., Authors' Conclusions: Further research is required to allow decisions about implementation of binocular treatments for amblyopia in clinical practice. Currently there are no clinical trials offering standardised evidence of the safety and effectiveness of binocular treatments, but results from non-controlled cohort studies are encouraging. Future research should be conducted in the form of RCTs, using acknowledged methods of visual acuity and stereoacuity assessment with known reproducibility. Other important outcome measures include outcomes reported by users, compliance with treatment, and recurrence of amblyopia after cessation of treatment.