Neuroplasticity and amblyopia: vision at the balance point

Purpose of review: New insights into triggers and brakes of plasticity in the visual system are being translated into new treatment approaches which may improve outcomes not only in children, but also in adults. / Recent findings: Visual experience-driven plasticity is greatest in early childhood, triggered by maturation of inhibitory interneurons which facilitate strengthening of synchronous synaptic connections, and inactivation of others. Normal binocular development leads to progressive refinement of monocular visual acuity, stereoacuity and fusion of images from both eyes. At the end of the ‘critical period’, structural and functional brakes such as dampening of acetylcholine receptor signalling and formation of perineuronal nets limit further synaptic remodelling. Imbalanced visual input from the two eyes can lead to imbalanced neural processing and permanent visual deficits, the commonest of which is amblyopia. / Summary: The efficacy of new behavioural, physical and pharmacological interventions aiming to balance visual input and visual processing have been described in humans, and some are currently under evaluation in randomised controlled trials. Outcomes may change amblyopia treatment for children and adults, but the safety of new approaches will need careful monitoring, as permanent adverse events may occur when plasticity is re-induced after the end of the critical period

Eye movements elevate crowding in idiopathic infantile nystagmus syndrome

Idiopathic infantile nystagmus syndrome is a disorder characterised by involuntary eye movements, which leads to decreased acuity and visual function. One such function is visual crowding - a process whereby objects that are easily recognised in isolation become impaired by nearby flankers. Crowding typically occurs in the peripheral visual field, although elevations in foveal vision have been reported in congenital nystagmus, similar to those found with amblyopia. Here, we examine whether elevated foveal crowding with nystagmus is driven by similar mechanisms to those of amblyopia - long-term neural changes associated with a sensory deficit - or by the momentary displacement of the stimulus through nystagmus eye movements. A Landolt-C orientation identification task was used to measure threshold gap sizes with and without either horizontally or vertically placed Landolt-C flankers. We assume that a sensory deficit should give equivalent crowding in these two dimensions, whereas an origin in eye movements should give stronger crowding with horizontal flankers given the predominantly horizontal eye movements of nystagmus. We observe elevations in nystagmic crowding that are above crowding in typical vision but below that of amblyopia. Consistent with an origin in eye movements, elevations were stronger with horizontal than vertical flankers in nystagmus, but not in typical or amblyopic vision. We further demonstrate the same horizontal elongation in typical vision with stimulus movement that simulates nystagmus. Consequently, we propose that the origin of nystagmic crowding lies in the eye movements, either through image smear of the target and flanker elements or through relocation of the stimulus into the peripheral retina

Steroid-sparing effect of ciclosporin A 1 mg/mL: 5-year case series of 107 children and young people with vernal keratoconjunctivitis

Background/aims To explore the steroid-sparing and other therapeutic effects of ciclosporin A (CsA) 1 mg/mL in the management of vernal keratoconjunctivitis (VKC). Methods Open retrospective single-group interventional consecutive cohort study (case series) of 107 children and young people (CYP) age 4.4-18 years with severe and/or recurrent VKC who were prescribed CsA 1 mg/mL between November 2015 and May 2021 at one institution. Review of electronic patient records, noting clinical indication for prescribing CsA 1 mg/mL, dosage prescribed at initiation and follow-up, impact on steroid usage before and after commencing CsA as well as adverse events and indications for discontinuation of treatment. Results The median number of inflammatory episodes requiring treatment with topical corticosteroids fell from 3 (IQR 2-4) during the 12 months prior to CsA 1 mg/mL to 1 (IQR 0-3) during the 12 months after, excluding steroid prescriptions with the first CsA 1 mg/mL prescription (Wilcoxon signed ranks test, two tailed, p<0.01). In the 12-month period following initiation of CsA 1 mg/mL with concomitant prescription of topical corticosteroids (n=82), daily dosage of steroids was reduced in 79 (96.3%) and discontinued in 67 (81.7%). The median number of hospital clinic visits fell from 4 (IQR 3-5) to 3 (IQR 2-5) (Wilcoxon p<0.01). Adverse events leading to discontinuation of CsA 1 mg/mL within 12 months of starting included stinging (instillation site pain) (6/107, 5.6%) and skinrash (1/107, 0.9%). Conclusion Commercial preparations of CsA 1 mg/mL, licensed for severe VKC in CYP, significantly reduce the need for concomitant topical corticosteroids and hospital clinic visits. Adverse events which may lead to discontinuation are stinging and skin rash

Medically unexplained visual loss in children and young people: an observational single site study of incidence and outcomes

Purpose To determine the incidence of medically unexplained visual loss (MUVL) in children in an open access children’s eye casualty. Patients and methods We collated demographic and clinical data of consecutive patients younger than 16 years who presented to the children’s eye casualty at Moorfields Eye Hospital over a 12-month period and were diagnosed with MUVL or suspected MUVL. We reviewed the clinical records at least 3 months after initial presentation. We calculated the incidence using the number of ‘new patient’ attendances over the same period as denominator (n=2397). We used descriptive analysis. Main outcome measures: number of patients diagnosed with MUVL, proportion of patients with a history of or present psychological problems, recovery rate, and improvement in visual acuity. Results We identified 85 cases of MUVL (54 females; median age: 9 years (IQR 7–12)). The median duration of follow-up was 1.2 months (IQR 0–4.3). The estimated annual incidence was 3.5% (95% confidence interval 2.9–4.4%). Thirty-three per cent of children had a history of psychiatric disorders, reported a stressful life event, or showed signs of psychiatric disorder at the time of first presentation. The recovery rate was 25%. Median improvement in best-corrected visual acuity from presentation to last appointment was 0.22 (IQR 0.06–0.43) logMAR. Conclusion The incidence of MUVL is higher and the rate of resolution lower than previously reported. MUVL may be associated with mental health problems. We recommend screening for psychological problems to facilitate access to psychological treatment

Optical Coherence Tomography Findings After Childhood Lensectomy

Purpose: To explore the impact of childhood lensectomy on posterior segment development. / Methods: Cross-sectional observational study at children's eye clinics at a tertiary referral center in London, UK. We included 45 children age 4 to 16 years with healthy eyes and 38 who had undergone lensectomy. We acquired posterior segment optical coherence tomography scans of both eyes. We used parametric and nonparametric tests in SPSS24 for the comparison of parameters between groups and within individuals; a P value less than 0.05 was considered significant. The main outcome measures were foveal pit depth and subfoveal choroidal thickness (CT). Secondary outcomes were inner and outer ring CT and photoreceptor layer parameters, macular and peripapillary retinal nerve fiber layer thickness. / Results: Foveal pit depth and subfoveal CT are significantly reduced in eyes that have undergone lensectomy compared with nonoperated eyes. Inner ring CT and outer ring CT are reduced. Foveal inner retinal layer thickness is increased. Mean inner retinal and outer nuclear layer thickness are not affected. / Conclusions: Childhood lensectomy is associated with a reduction in developmental foveal pit deepening and lack of developmental thickening of the posterior choroid. Mechanical and optical disruption of foveal and subfoveal choroidal development may affect structural foveal development after childhood lensectomy

Childhood lensectomy is associated with static and dynamic reduction in Schlemm canal size: a biomechanical hypothesis of post-lensectomy glaucoma

OBJECTIVE: To compare Schlemm canal (SC) and trabecular meshwork (TM) in children with healthy eyes and those with and without glaucoma after lensectomy. DESIGN: Cross-sectional observational study. PARTICIPANTS: Fifty children age 4 to 16 years with healthy eyes and 48 children post lensectomy (124 healthy and 72 post-lensectomy eyes). METHODS: /Interventions: Anterior segment optical coherence tomography (AS-OCT, Tomey Casia) of the nasal iridocorneal angle, at two levels of accommodative effort (2.5D, 15D). For each parameter and state of accommodation, a random-effects model was fitted to estimate differences between healthy eyes and eyes with history of lensectomy. MAIN OUTCOME MEASURES: Dimensions of SC and TM; conventional AS-OCT irido-corneal angle (ICA) measurements. RESULTS: The horizontal diameter of SC and its cross-sectional area (SC-CSA) are significantly smaller in post-lensectomy than in healthy eyes. Accommodative effort increases SC size in healthy, but not in post-lensectomy eyes. CONCLUSIONS: Lensectomy is associated with a reduction in SC size and a loss of physiological SC dilatation during accommodative effort, which may reflect a reduction in outflow facility and contribute to the development of post-lensectomy glaucoma

Design and descriptive results of the "Growth, Exercise and Nutrition Epidemiological Study In preSchoolers": The GENESIS Study

BACKGROUND: The Growth, Exercise and Nutrition Epidemiological Study in preSchoolers (GENESIS) attempts to evaluate the food and nutrient intakes, as well as growth and development of a representative sample of Greek toddlers and preschool children. In the current work the study design, data collection procedures and some preliminary data of the GENESIS study are presented. METHODS: From April 2003 to July 2004, 1218 males and 1156 females 1 to 5 years old, stratified by parental educational level (Census 1999), were examined from 105 nurseries in five counties. Approximately 300 demographic, lifestyle, physical activity, dietary, anthropometrical and DNA variables have been recorded from the study population (children and parents). RESULTS: Regarding anthropometrical indices, boys were found to be taller than girls at all ages (P < 0.05) and heavier only for the age period from 1 to 3 years old (P < 0.05). No significant differences were found between genders regarding the prevalence of at risk of overweight (16.5% to 18.6% for boys and 18.5 to 20.6 % for girls) and overweight (14.0% to 18.9% for boys and 12.6% to 20.0% for girls). Additionally, boys older than 2 years of age were found to have a higher energy intake compared to girls (P < 0.05). A similar tendency was observed regarding the mean dietary intake of fat, saturated fat, carbohydrates and protein with boys exhibiting a higher intake than girls in most age groups (P < 0.05). CONCLUSION: The prevalence of overweight in the current preschool population is considerably high. Future but more extensive analyses of the GENESIS data will be able to reveal the interactions of the parameters leading to this phenomenon

Receptor-targeted liposome-peptide-siRNA nanoparticles represent a novel and efficient therapeutic approach to prevent conjunctival fibrosis.

There is increasing evidence that the Myocardin-related transcription factor/Serum response factor (MRTF/SRF) pathway plays a key role in fibroblast activation and that knocking down MRTF can lead to reduced scarring and fibrosis. Here, we have developed a receptor-targeted liposome-peptide-siRNA nanoparticle as a non-viral delivery system for MRTF-B siRNA in conjunctival fibrosis. Using 50 nM siRNA, the MRTF-B gene was efficiently silenced by 76% and 72% with LYR and LER nanoparticles, respectively. The silencing efficiency was low when non-targeting peptides or siRNA alone or liposome-siRNA alone were used. LYR and LER nanoparticles also showed higher silencing efficiency than PEGylated LYR-P and LER-P nanoparticles. The nanoparticles were not cytotoxic using different liposomes, targeting peptides, and 50 nM siRNA. Three-dimensional fibroblast-populated collagen matrices were also used as a functional assay to measure contraction in vitro, and showed that MRTF-B LYR nanoparticles completely blocked matrix contraction after a single transfection treatment. In conclusion, this is the first study to develop and show that receptor-targeted liposome-peptide-siRNA nanoparticles represent an efficient and safe non-viral siRNA delivery system that could be used to prevent fibrosis after glaucoma filtration surgery and other contractile scarring conditions in the eye

Attentional Performance in Children and Adolescents with Tic Disorder and Co-Occurring Attention-Deficit/Hyperactivity Disorder: New Insights from a 2 × 2 Factorial Design Study

The aim of the present study was to investigate the effect of both tic disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) on attentional functions. N = 96 children and adolescents participated in the study, including n = 21 subjects with TD, n = 23 subjects with ADHD, n = 25 subjects with TD+ADHD, and n = 27 controls. Attentional performance was tested based on four computerized attention tasks (sustained attention, divided attention, go/nogo and set shifting). The effect of TD as well as ADHD on attentional performance was tested using a 2 × 2 factorial approach. A diagnosis of TD had no negative impact on attentional functions but was associated with improved performance in the set shifting task. By contrast, regardless of a diagnosis of TD, subjects with ADHD were found to perform worse in the sustained attention, divided attention and go/nogo task. No interaction effect between the factors TD and ADHD was revealed for any of the attention measures. Our results add to findings from other areas of research, showing that in subjects with TD and ADHD, ADHD psychopathology is often the main source of impairment, whereas a diagnosis of TD has little or no impact on neuropsychological performance in most cases and even seems to be associated with adaptive mechanisms