Commercial Versus Compounded Preparations in Pediatric Ophthalmology.

Many conditions managed by pediatric ophthalmologists are rare diseases, and even if pharmacological treatments are available, these have often not been evaluated in children. Off-label prescribing is a common practice in pediatric ophthalmology. In addition, there is often no commercial case for the production of a medicine that may only be used for a small number of patients worldwide. Compounded preparations prepared locally are therefore still in frequent use, although it is known that production may not meet stringent quality assurance standards. For several indications, commercial preparations, evaluated in rigorous clinical trials with children, are now available. Myopia management is joining the list of these indications, with low-concentration atropine formulations derived from recent clinical trials in Australia, USA, and Europe now entering the market. This short article gives an overview of the background and recent developments of compounded and commercial preparations for use in pediatric ophthalmology.

Extended optical treatment versus early patching with an intensive patching regimen in children with amblyopia in Europe (EuPatch): a multicentre, randomised controlled trial.

BACKGROUND: Amblyopia, the most common visual impairment of childhood, is a public health concern. An extended period of optical treatment before patching is recommended by the clinical guidelines of several countries. The aim of this study was to compare an intensive patching regimen, with and without extended optical treatment (EOT), in a randomised controlled trial. METHODS: EuPatch was a randomised controlled trial conducted in 30 hospitals in the UK, Greece, Austria, Germany, and Switzerland. Children aged 3-8 years with newly detected, untreated amblyopia (defined as an interocular difference ≥0·30 logarithm of the minimum angle of resolution [logMAR] best corrected visual acuity [BCVA]) due to anisometropia, strabismus, or both were eligible. Participants were randomly assigned (1:1) via a computer-generated sequence to either the EOT group (18 weeks of glasses use before patching) or to the early patching group (3 weeks of glasses use before patching), stratified for type and severity of amblyopia. All participants were initially prescribed an intensive patching regimen (10 h/day, 6 days per week), supplemented with motivational materials. The patching period was up to 24 weeks. Participants, parents or guardians, assessors, and the trial statistician were not masked to treatment allocation. The primary outcome was successful treatment (ie, ≤0·20 logMAR interocular difference in BCVA) after 12 weeks of patching. Two primary analyses were conducted: the main analysis included all participants, including those who dropped out, but excluded those who did not provide outcome data at week 12 and remained on the study; the other analysis imputed this missing data. All eligible and randomly assigned participants were assessed for adverse events. This study is registered with the International Standard Randomised Controlled Trial Number registry (ISRCTN51712593) and is no longer recruiting. FINDINGS: Between June 20, 2013, and March 12, 2020, after exclusion of eight participants found ineligible after detailed screening, we randomly assigned 334 participants (170 to the EOT group and 164 to the early patching group), including 188 (56%) boys, 146 (44%) girls, and two (1%) participants whose sex was not recorded. 317 participants (158 in the EOT group and 159 in the early patching group) were analysed for the primary outcome without imputation of missing data (median follow-up time 42 weeks [IQR 42] in the EOT group vs 27 weeks [27] in the early patching group). 24 (14%) of 170 participants in the EOT group and ten (6%) of 164 in the early patching group were excluded or dropped out of the study, mostly due to loss to follow-up and withdrawal of consent; ten (6%) in the EOT group and three (2%) in the early patching group missed the 12 week visit but remained on the study. A higher proportion of participants in the early patching group had successful treatment (107 [67%] of 159) than those in the EOT group (86 [54%] of 158; 13% difference; p=0·019) after 12 weeks of patching. No serious adverse events related to the interventions occurred. INTERPRETATION: The results from this trial indicate that early patching is more effective than EOT for the treatment of most children with amblyopia. Our findings also provide data for the personalisation of amblyopia treatments. FUNDING: Action Medical Research, NIHR Clinical Research Network, and Ulverscroft Foundation.

Low concentration atropine and myopia: a narrative review of the evidence for United Kingdom based practitioners.

The prevalence of myopia is increasing across the world. Controlling myopia progression would be beneficial to reduce adverse outcomes such as retinal detachment and myopic maculopathy which are associated with increased axial length. Pharmacological control of myopia progression with atropine has been investigated since the 19th century and the benefits of slowing myopia progression are considered against the side-effects of near blur and photophobia. More recently, randomised trials have focused on determining the optimum concentration of atropine leading to low-concentration atropine being used to manage myopia progression by practitioners across the world. Currently, in the United Kingdom, there is no licensed pharmacological intervention for myopia management. The aim of this review is to interpret the available data to inform clinical practice. We conducted a narrative review of the literature and identified peer-reviewed randomised controlled trials using the search terms 'myopia' and 'atropine', limited to the English language. We identified two key studies, which were the Atropine in the Treatment Of Myopia (ATOM) and Low-concentration Atropine for Myopia Progression (LAMP). Further studies were identified using the above search terms and the references from the identified literature. Atropine 0.01% has a modest effect on controlling axial length progression. Atropine 0.05% appears to be superior to atropine 0.01% in managing myopia progression. There is a dose-dependent rebound effect when treatment is stopped. Atropine is a well-tolerated, safe, and effective intervention. Treatment would be needed for several years and into adolescence, until axial length progression is stable.

Definition and Diagnostic Criteria for Pediatric Blepharokeratoconjunctivitis.

Importance: Pediatric blepharokeratoconjunctivitis (PBKC) is a chronic, sight-threatening inflammatory ocular surface disease. Due to the lack of unified terminology and diagnostic criteria, nonspecific symptoms and signs, and the challenge of differentiation from similar ocular surface disorders, PBKC may be frequently unrecognized or diagnosed late. Objective: To establish a consensus on the nomenclature, definition, and diagnostic criteria of PBKC. Design, Setting, and Participants: This quality improvement study used expert panel and agreement applying the non-RAND modified Delphi method and open discussions to identify unified nomenclature, definition, and definitive diagnostic criteria for PBKC. The study was conducted between September 1, 2021, and August 14, 2022. Consensus activities were carried out through electronic surveys via email and online virtual meetings. Results: Of 16 expert international panelists (pediatric ophthalmologists or cornea and external diseases specialists) chosen by specific inclusion criteria, including their contribution to scientific leadership and research in PBKC, 14 (87.5%) participated in the consensus. The name proposed was "pediatric blepharokeratoconjunctivitis," and the agreed-on definition was "Pediatric blepharokeratoconjunctivitis is a frequently underdiagnosed, sight-threatening, chronic, and recurrent inflammatory eyelid margin disease associated with ocular surface involvement affecting children and adolescents. Its clinical spectrum includes chronic blepharitis, meibomitis, conjunctivitis, and corneal involvement ranging from superficial punctate keratitis to corneal infiltrates with vascularization and scarring." The diagnostic criteria included 1 or more suggestive symptoms accompanied by clinical signs from 3 anatomical regions: the eyelid margin, conjunctiva, and cornea. For PBKC suspect, the same criteria were included except for corneal involvement. Conclusions and Relevance: The agreements on the name, definition, and proposed diagnostic criteria of PBKC may help ophthalmologists avoid diagnostic confusion and recognize the disease early to establish adequate therapy and avoid sight-threatening complications. The diagnostic criteria rely on published evidence, analysis of simulated clinical cases, and the expert panel's clinical experience, requiring further validation with real patient data analysis.

Can children measure their own vision? A comparison of three new contrast sensitivity tests.

PURPOSE: To investigate the feasibility of children measuring their own contrast sensitivity using a range of tablet- and paper-based tests. METHODS: Forty children aged 5-15 years with amblyopia (N = 10), bilateral vision impairment (N = 10) or good vision (N = 20) measured their own vision on a screen-based optotype test (Manifold), a gamified vision test (PopCSF) and a paper-based test (Spotchecks) in a laboratory with minimal supervision. Completion rate, test-retest repeatability, test duration and participants' preferences were recorded for each test. RESULTS: Most participants (36/40) were able to perform all three tests. All tests were correlated with clinically measured visual acuity and contrast sensitivity (p < 0.001). The 95% coefficient of repeatability was 0.30 dB for Manifold, 0.29 dB for PopCSF and 0.13 dB for Spotchecks. All tests differentiated between children with reduced contrast sensitivity and control participants. PopCSF and Spotchecks were also able to differentiate between children with amblyopia and those with good vision. Median test time was 152, 130 and 202 s for Manifold, PopCSF and Spotchecks, respectively. Twenty-two participants preferred the PopCSF test, 10 preferred Spotchecks and 6 preferred Manifold. Thirty-nine out of the 40 children (98%) said they would measure their own vision at home using at least one of these tests every month. CONCLUSIONS: Children and young people can test their own contrast sensitivity with repeatable results. Of these three tests, the most repeatable was Spotchecks, the quickest was PopCSF and participants' favourite was PopCSF. Nearly all of the participants said they would be willing to use at least one of the three tests at home.

Usability of an Eye Drop Delivery Aid for Single-Dose Instillation: Results from a Market Research Study.

Background: One of the challenges of treating chronic ocular diseases like vernal keratoconjunctivitis (VKC), glaucoma, and ocular surface disease is patient adherence to topical medication. To support correct eye drop instillation, a variety of delivery aids have been developed for both single-dose and conventional multi-dose containers. Methods: To evaluate Dropaid™ Single-dose, an eye drop delivery aid designed for single-dose containers, a usability study was conducted on 30 parents and caregivers of patients with VKC. After assessing the ability to squeeze a single eye drop from the single-dose container onto the eye of a pediatric medical dummy, the delivery aid was evaluated using an 11-point Likert scale on a variety of characteristics: from "very difficult" (-5) to "very easy" (+5). Results: The majority of participants rated the task of opening the single-dose units (SDUs), preparing, and positioning the Dropaid™ Single-dose device as "very easy". When providing a single eye drop from the container, 87% of participants rated the Dropaid™ Single-dose device as either "very easy" or "easy", with a median rating score of +5.0 (interquartile range [IQR], 4.0-5.0). For general ease of use, 84% considered the delivery aid as either "very easy" or "easy", with a median score of +4.0 (IQR, 3.0-5.0). Most participants (93%) rated Dropaid™ Single-dose as either "very comfortable" or "comfortable" to hold, with a median score of +5.0 (IQR, 4.0-5.0). Conclusion: The Dropaid™ Single-dose delivery aid demonstrated rapid learning and ease of use across all stages of application, including opening the container, eye drop administration, and handling comfort. Although designed for use with single-dose containers to help eye drop instillation in patients with VKC, Dropaid™ Single-dose may provide a wider utility across a range of other ocular diseases such as glaucoma and dry eye.

Amblyopia-A novel virtual round table to explore the caregiver perspective.

PURPOSE: A survey aimed to capture the caregiver's perspective on the impact of amblyopia and its treatment on the child and family, as well as caregivers' views on the design and feasibility of clinical trials investigating dichoptic binocular therapies for amblyopia. METHODS: Parents of amblyopic children, patient advocates and healthcare professionals took part in a moderated, structured discussion on a novel virtual advisory-board platform. RESULTS: Seven parents of children with amblyopia, two patient organisation representatives, one ophthalmologist and one optometrist participated in the survey. A total of 645 posts were entered on the platform over a 14-day period in September 2021. There was widespread agreement that the management of amblyopia poses more of a burden on the child and family than the condition itself, with treatment burden accentuated when treatment is unsuccessful. Parents expressed uncertainty and frustration in relation to the duration of patching, success of patching and alternative treatment options, and felt there was inadequate readily available, easy-to-understand information on the condition. Parents reported that a new treatment for amblyopia, such as dichoptic binocular therapy using video games, should be safe, non-invasive and engaging compared with an eye patch. Treating at home, potentially for a shorter treatment duration, and with an entertaining game were the main reasons parents would join a clinical study with this type of novel therapy. However, due to a limited critical period treatment window, parents would feel more comfortable joining a clinical trial if traditional therapies were offered in conjunction with those under investigation. CONCLUSION: Patient perspectives and the role of caregivers in the acceptance of any interventional treatments are increasingly recognised. Understanding how amblyopia and its treatment impacts a child and family should be an important premise to guide therapy and evaluate treatment value, both in clinical trials and in routine medical practice.

Providing multimedia information to children and young people increases recruitment to trials: pre-planned meta-analysis of SWATs.

BACKGROUND: Randomised controlled trials are often beset by problems with poor recruitment and retention. Information to support decisions on trial participation is usually provided as printed participant information sheets (PIS), which are often long, technical, and unappealing. Multimedia information (MMI), including animations and videos, may be a valuable alternative or complement to a PIS. The Trials Engagement in Children and Adolescents (TRECA) study compared MMI to PIS to investigate the effects on participant recruitment, retention, and quality of decision-making. METHODS: We undertook six SWATs (Study Within A Trial) within a series of host trials recruiting children and young people. Potential participants in the host trials were randomly allocated to receive MMI-only, PIS-only, or combined MMI + PIS. We recorded the rates of recruitment and retention (varying between 6 and 26 weeks post-randomisation) in each host trial. Potential participants approached about each host trial were asked to complete a nine-item Decision-Making Questionnaire (DMQ) to indicate their evaluation of the information and their reasons for participation/non-participation. Odds ratios were calculated and combined in a meta-analysis. RESULTS: Data from 3/6 SWATs for which it was possible were combined in a meta-analysis (n = 1758). Potential participants allocated to MMI-only were more likely to be recruited to the host trial than those allocated to PIS-only (OR 1.54; 95% CI 1.05, 2.28; p = 0.03). Those allocated to combined MMI + PIS compared to PIS-only were no more likely to be recruited to the host trial (OR = 0.89; 95% CI 0.53, 1.50; p = 0.67). Providing MMI rather than PIS did not impact on DMQ scores. Once children and young people had been recruited to host trials, their trial retention rates did not differ according to intervention allocation. CONCLUSIONS: Providing MMI-only increased the trial recruitment rate compared to PIS-only but did not affect DMQ scores. Combined MMI + PIS instead of PIS had no effect on recruitment or retention. MMIs are a useful tool for trial recruitment in children and young people, and they could reduce trial recruitment periods.

"We know that our voices are valued, and that people are actually going to listen": co-producing an evaluation of a young people's research advisory group.

BACKGROUND: Children and young people's (CYP) involvement is an increasing priority in UK healthcare and in heath research, alongside recognition that involving CYP in research requires different considerations to involving adults. Underpinned by children's rights and a co-production ethos this paper, co-authored with young evaluators, explores the learning from a co-produced evaluation of eyeYPAG, a young persons' research advisory group (YPAG) for eye and vision research based at Moorfields Eye Hospital, London, UK. METHODS: A team of young evaluators, supported by the eyeYPAG facilitator, conducted focus groups and online surveys with YPAG members, their parents and carers, researchers, group facilitators and funders. Qualitative data was analysed using a collaborative reflexive thematic analysis approach. Quantitative data, limited by the small number of participants, was analysed in Excel and reported as descriptive data. RESULTS: CYP valued the social and creative aspects of the group as well as learning about research and developing skills and confidence. Learning was a two-way process, with both researchers and facilitators reflecting on how much they had learnt from working with the YPAG. All participants talked about the importance of impact, feeling that CYP are making a difference to research, as well as CYP's right to be involved. Effective planning and facilitation were key to the success of the group, in relation to accessibility and the development and delivery of sessions both online and in-person. Resourcing and administration were key challenges to this, as was engaging researchers who were not already converted to the public involvement cause. As the nature of a YPAG is that it primarily focuses on advising researcher-led projects, co-production was identified as something that the group was 'working towards', including through this evaluation. Co-producing with CYP involves building up knowledge, confidence and acknowledging power dynamics. CONCLUSIONS: Co-producing an evaluation enabled us to learn about the benefits and challenges of involving CYP in research, as well as how to involve them in the development of that evidence. An ethos of co-production and children's rights helped to shift the balance of power and develop more engaging and inclusive ways of working.

Children and young people (CYP) have a right to be involved in things that affect them, including research. There is growing interest in children and young people's involvement in health research in the United Kingdom (UK), as well as understanding that what works for CYP is often different to what works for adults. This paper presents an evaluation of the Young Person's Advisory Group (YPAG) at Moorfields Eye Hospital in London. Evaluation uses research methods to find out how well a service or project is working and meeting the needs of those who use it, and how to improve things that could be better. A group of young evaluators, supported by adult researchers, designed and ran the evaluation; three of the young evaluators also helped write this paper. In our evaluation we used focus (discussion) groups and online surveys with young group members, their parents and carers, researchers who had worked with the group, the group's facilitators (adults who help manage the group) and funders. We found that group members valued the social and creative aspects of the group as well as learning about research and developing skills and confidence. Learning was a two-way process, with both researchers and facilitators talking about how much they had learnt from working with the YPAG. All participants talked about the importance of feeling that CYP are making a difference to research, as well as of CYP's right to be involved. Planning and support were important to the group working well, but we found that having the money and time to do this well was not always easy. And, while lots of researchers were keen to work with the group, and talked about how this had helped their research, we need to do more to engage researchers who have yet to be convinced. We also found that, while we wanted to 'co-produce' the group and share power for all big decisions, this was something we had to work towards, especially when group members were young and/or new to research and involvement. Co-producing an evaluation helped us to learn about the benefits and challenges of involving CYP in research, as well as how to involve them in evaluating that involvement.

Novel Insights in the Management of Vernal Keratoconjunctivitis (VKC): European Expert Consensus Using a Modified Nominal Group Technique.

INTRODUCTION: Vernal keratoconjunctivitis (VKC) is a rare, severe allergic ocular disease, typically occurring in children and adolescents, that can have a significant impact on quality of life and lead to visual impairment. Long-term treatment may be necessary to tackle chronic inflammation and topical corticosteroid dependency must be minimised due to the risk of complications. There is a need for unified clinical guidance to aid the assessment, diagnosis and management of VKC across Europe. The aim of this expert panel (the EUR-VKC Group) was to provide clear guidance for primary care physicians and general ophthalmologists involved in the diagnosis and management of VKC. METHODS: An expert group of seven European ophthalmologists was convened and a modified nominal group technique used to develop key recommendations on VKC management. The recommendations were subject to up to two rounds of voting using a 5-point Likert scale to ascertain consensus and the strength of each recommendation. Consensus was set at a predetermined threshold of ≥ 75.0% of experts selecting 'Strongly agree' or 'Agree'. RESULTS: A total of 47 recommendations were developed relating to the assessment of key of VKC, guidance on who and when to refer, as well as treatment-escalation pathways, long-term follow-up, and supportive care and education. All recommendations reached consensus after two rounds. The group emphasise how timely diagnosis and treatment initiation that is appropriate to disease severity are crucial to benefit patients with VKC. Patients with signs ('red flags') indicating severe VKC, or persistent mild-to-moderate VKC that is non-responsive following 2-4 weeks of treatment, should be referred to a sub-specialist. CONCLUSION: The EUR-VKC Group provides recommendations on the assessment, diagnosis, management, referral and follow-up of patients with VKC. It also provides a framework to facilitate collaboration between primary care physicians, general ophthalmologists and sub-specialists to improve the outcomes for patients with VKC.

Vernal keratoconjunctivitis (VKC) is a rare, underdiagnosed, chronic allergic eye disease that typically occurs in children and adolescents. If left untreated, VKC can significantly damage the eye, potentially leading to long-term complications, visual impairment and a reduced quality of life for the child and their family and/or caregivers. In the absence of established guidelines, this consensus programme set out to gather expert insights on best practices for assessing and managing VKC across Europe. A group of seven European ophthalmologists engaged in the consensus programme. A total of 47 recommendations were developed relating to the assessment, diagnosis, management, referral and follow-up of patients with VKC. These 47 recommendations underwent two rounds of review and were revised, if necessary, following expert input. Recommendations where ≥ 75.0% of experts agreed were considered as having reached consensus and were included as final recommendations. The experts agreed that VKC can be classified as mild, moderate or severe, and should be managed according to severity in a stepwise manner, with treatment intensity escalating as the disease severity increases. Timely diagnosis and treatment initiation appropriate to the severity of VKC are crucial to prevent sight loss and improve the quality of life of children with VKC. Ongoing treatment may be necessary to tackle the chronic inflammation associated with the disease and, therefore, reliance on steroid eye drops should be reduced to avoid an increased risk of well-known complications. The experts concluded that mild VKC can be assessed and managed in primary care, but patients with severe VKC, or with moderate-to-severe VKC that does not respond to treatment within 2­4 weeks, should be referred to a VKC specialist.

Paediatric eye and vision research participation experiences: a systematic review.

BACKGROUND: For children and young people with eye and vision conditions, research is essential to advancing evidence-based recommendations in diagnosis, prevention, treatments and cures. Patient 'experience' reflects a key measure of quality in health care (Department of Health. High Quality Care for All: NHS Next Stage Review Final Report: The Stationery Office (2008)); research participant 'experiences' are equally important. Therefore, in order to achieve child-centred, high-quality paediatric ophthalmic research, we need to understand participation experiences. We conducted a systematic review of existing literature; our primary outcome was to understand what children and young people, parents and research staff perceive to support or hinder positive paediatric eye and vision research experiences. Our secondary outcomes explored whether any adverse or positive effects were perceived to be related to participation experiences, and if any interventions to improve paediatric ophthalmic research experiences had previously been developed or used. METHODS: We searched (from inception to November 2018, updated July 2020) in MEDLINE, Embase, CINAHL, Web of Science, NICE evidence and The Cochrane Library (CDSR and CENTRAL), key journals (by hand), grey literature databases and Google Scholar; looking for evidence from the perspectives of children, young people, parents and staff with experience of paediatric ophthalmic research. The National Institute for Health Research (NIHR) Participant in Research Experience Survey (PRES) (National Institute for Health Research. Research Participant Experience Survey Report 2018-19 (2019); National Institute for Health Research. Optimising the Participant in Research Experience Checklist (2019)) identified 'five domains' pivotal to shaping positive research experiences; we used these domains as an 'a priori' framework to conduct a 'best fit' synthesis (Carroll et al., BMC Med Res Methodol. 11:29, 2011; Carroll et al., BMC Med Res Methodol. 13:37, 2013). RESULTS: Our search yielded 13,020 papers; two studies were eligible. These evaluated research experiences from the perspectives of parents and staff; the perspectives of children and young people themselves were not collected. No studies were identified addressing our secondary objectives. Synthesis confirmed the experiences of parents were shaped by staff characteristics, information provision, trial organisation and personal motivations, concurring with the 'PRES domains' (National Institute for Health Research. Optimising the Participant in Research Experience Checklist (2019)) and generating additional dimensions to participation motivations and the physical and emotional costs of study organisation. CONCLUSIONS: The evidence base is limited and importantly omits the voices of children and young people. Further research, involving children and young people, is necessary to better understand the research experiences of this population, and so inform quality improvements for paediatric ophthalmic research care and outcomes. TRIAL REGISTRATION: Review registered with PROSPERO, International prospective register of systematic reviews: CRD42018117984. Registered on 11 December 2018.

Management of Vernal Keratoconjunctivitis in Children in the United Kingdom: A Review of the Literature and Current Best Practice Across Six Large United Kingdom Centers.

Vernal keratoconjunctivitis (VKC) is a form of ocular allergy primarily affecting children. Considered a rare disease in Europe, its prevalence varies by geographic region and is poorly studied in the United Kingdom. There is considerable national variation in the management of VKC within the United Kingdom, risking misdiagnosis and delays to treatment for some children. This can significantly impact their quality of life, with the potential for lasting negative consequences. Based on discussions between experienced clinicians from six large centers across the United Kingdom, this article describes best practice recommendations for United Kingdom settings, including principles for diagnosis, referral, initial and long-term management, and supportive care. Recommendations include guidance on referral timing, which should depend on VKC severity, and a stepwise approach to treatment. Joint management by primary care and secondary care is recommended and the importance of supportive care, including emotional support and outreach to schools, is highlighted. Because frequent flareups are common in VKC, it is essential that families have access to the information they need to manage the disease and routes to access rapid care if needed. A thorough understanding of the nature of VKC, its triggers, and how best to manage it, by both patients and their families, is critical to ensuring appropriate management and to improving patient outcomes. [J Pediatr Ophthalmol Strabismus. 2023;60(1):6-17.].

Topical cyclosporine A 1 mg/ml for atopic keratoconjunctivitis: Five-year case series of 99 children and young people.

PURPOSE: To explore the effects of cyclosporine A (CsA) in the management of atopic keratoconjunctivitis (AKC). METHODS: Open single-group interventional consecutive cohort study (case series) at a single eye care facility in the UK. We reviewed the electronic patient records of 99 children and young people (CYP) aged 3.4-18 years with AKC treated with topical CsA 1 mg/ml. Main outcome measures were number of prescriptions and hospital clinic visits over 12 months before and after the start of CsA and the proportion of CYP affected by adverse effects. RESULTS: The median number of inflammatory episodes requiring treatment with topical corticosteroids (tCS) fell from 3 (interquartile range IQR 1-4) during the 12 months prior to CsA to 1 (IQR 0-3) during the 12 months after, excluding tCS prescriptions with the first CsA prescription (Wilcoxon signed ranks test, 2 tailed, p < 0.01). In the 12-month period following initiation of CsA 1 mg/ml with concomitant prescription of tCS (n = 66), daily dosage of steroids was reduced in 62 CYP (93.9%), and they were discontinued in 43 (65.2%). The median number of hospital visits fell from 4 (IQR 3-6) to 3 (IQR 2-5; Wilcoxon p < 0.01). Adverse events leading to discontinuation of CsA were stinging (instillation site pain; 9/99, 9%) and a transient skin rash (1/99, 1%). CONCLUSIONS: Off-label use of commercial preparations of CsA 1 mg/ml significantly reduces the need for concomitant topical corticosteroids and hospital clinic visits in CYP with AKC. Stinging and skin rash can lead to discontinuation.

Surgical interventions for bilateral congenital cataract in children aged two years and under.

BACKGROUND: Congenital cataracts are lens opacities in one or both eyes of babies or children present at birth. These may cause a reduction in vision severe enough to require surgery. Cataracts are proportionally the most treatable cause of visual loss in childhood, and are a particular problem in low-income countries, where early intervention may not be possible. Paediatric cataracts provide different challenges to those in adults. Intense inflammation, amblyopia (vision is obstructed by cataract from birth which prevents normal development of the visual system), posterior capsule opacification and uncertainty about the final trajectory of ocular growth parameters can affect results of treatment. Two options currently considered for children under 2 years of age with bilateral congenital cataracts are: (i) intraocular lens (IOL) implantation; or (ii) leaving a child with primary aphakia (no lens in the eye), necessitating the need for contact lenses or aphakic glasses. Other important considerations regarding surgery include the prevention of visual axis opacification (VAO), glaucoma and the route used to perform lensectomy. OBJECTIVES: To assess the effectiveness of infant cataract surgery or lensectomy to no surgery for bilateral congenital cataracts in children aged 2 years and under. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 1); Ovid MEDLINE; Ovid Embase; the ISRCTN registry; ClinicalTrials.gov and the WHO ICTRP. The date of the search was 25 January 2022. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared infant cataract surgery or lensectomy to no surgery, in children with bilateral congenital cataracts aged 2 years and younger. This update (of a review published in 2001 and updated in 2006) does not include children over 2 years of age because they have a wider variety of aetiologies, and are therefore managed differently, and have contrasting outcomes. DATA COLLECTION AND ANALYSIS: We used standard methods expected by Cochrane. Two review authors extracted data independently. We assessed the risk of bias of included studies using RoB 1 and assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified three RCTs that met our inclusion criteria with each trial comparing a different aspect of surgical intervention for this condition. The trials included a total of 79 participants under 2 years of age, were conducted in India and follow-up ranged from 1 to 5 years. Study participants and outcome assessors were not masked in these trials. One study (60 children) compared primary IOL implantation with primary aphakia. The results from this study suggest that there may be little or no difference in visual acuity at 5 years comparing children with pseudophakia (mean logMAR 0.50) and aphakia (mean logMAR 0.59) (mean difference (MD) -0.09 logMAR, 95% confidence intervals (CIs) -0.24 to 0.06; 54 participants; very low-certainty evidence), but the evidence is very uncertain. The evidence is very uncertain as to the effect of IOL implantation compared with aphakia on visual axis opacification (VAO) (risk ratio (RR) 1.29, 95% CI 0.23 to 7.13; 54 participants; very low-certainty evidence). The trial investigators did not report on the cases of amblyopia. There was little evidence of a difference betwen the two groups in cases of glaucoma at 5 years follow-up (RR 0.86, 95% CI 0.24 to 3.10; 54 participants; very low-certainty evidence). Cases of retinal detachment and reoperation rates were not reported. The impact of IOL implantation on adverse effects is very uncertain because of the sparse data available: of the children who were pseudophakic, 1/29  needed a trabeculectomy and 8/29 developed posterior synechiae. In comparison, no trabeculectomies were needed in the aphakic group and 2/25 children had posterior synechiae (54 participants; very low-certainty evidence).  The second study (14 eyes of 7 children under 2 years of age) compared posterior optic capture of IOL without vitrectomy versus endocapsular implantations with anterior vitrectomy (commonly called 'in-the-bag surgery'). The authors did not report on visual acuity, amblyopia, glaucoma and reoperation rate. They had no cases of VAO in either group. The evidence is very uncertain as to the effect of in-the-bag implantation in children aged under 1 year. There was a higher incidence of inflammatory sequelae: 4/7 in-the-bag implantation eyes and 1/7 in optic capture eyes (P = 0.04, 7 participants; very low-certainty evidence). We graded the certainty of evidence as low or very low for imprecision in all outcomes because their statistical analysis reported that a sample size of 13 was needed in each group to achieve a power of 80%, whereas their subset of children under the age of 1 year had only 7 eyes in each group. The third study (24 eyes of 12 children) compared a transcorneal versus pars plana route using a 25-gauge transconjunctival sutureless vitrectomy system. The evidence is very uncertain as to the effect of the route chosen on the incidence of VAO, with no cases reported at 1 year follow-up in either group. The investigators did not report on visual acuity, amblyopia, glaucoma, retinal detachment and reoperation rate. The pars plana route had the adverse effects of posterior capsule rupture in 2/12 eyes, and 1/12 eyes needing sutures. Conversely, 1/12 eyes operated on by the transcorneal route needed sutures. We graded the outcomes with very low-certainty because of the small sample size and the absence of a priori sample size calculation. AUTHORS' CONCLUSIONS: There is no high level evidence for the effectiveness of one type of surgery for bilateral congenital cataracts over another, or whether surgery itself is better than primary aphakia. Further RCTs are required to inform modern practice about concerns, including the timing of surgery, age at which surgery should be undertaken, age for implantation of an IOL and development of complications, such as reoperations, glaucoma and retinal detachment. Standardising the methods used to measure visual function, along with objective monitoring of compliance with the use of aphakic glasses/contact lenses would greatly improve the quality of study data and enable more reliable interpretation of outcomes.

Crowding changes appearance systematically in peripheral, amblyopic, and developing vision.

Visual crowding is the disruptive effect of clutter on object recognition. Although most prominent in adult peripheral vision, crowding also disrupts foveal vision in typically developing children and those with strabismic amblyopia. Do these crowding effects share the same mechanism? Here we exploit observations that crowded errors in peripheral vision are not random: Target objects appear either averaged with the flankers (assimilation) or replaced by them (substitution). If amblyopic and developmental crowding share the same mechanism, then their errors should be similarly systematic. We tested foveal vision in children aged 3 to 8 years with typical vision or strabismic amblyopia and peripheral vision in typical adults. The perceptual effects of crowding were measured by requiring observers to adjust a reference stimulus to match the perceived orientation of a target "Vac-Man" element. When the target was surrounded by flankers that differed by ± 30°, all three groups (adults and children with typical or amblyopic vision) reported orientations between the target and flankers (assimilation). Errors were reduced with ± 90° differences but primarily matched the flanker orientation (substitution) when they did occur. A population pooling model of crowding successfully simulated this pattern of errors in all three groups. We conclude that the perceptual effects of amblyopic and developing crowding are systematic and resemble the near periphery in adults, suggesting a common underlying mechanism.