Prospective study of pediatric patients presenting with idiopathic infantile nystagmus-Management and molecular diagnostics.

Idiopathic infantile nystagmus (IIN) is an inherited disorder occurring in the first 6 months of life, with no underlying retinal or neurological etiologies and is predominantly caused by mutations in the FRMD7 gene. IIN poses a diagnostic challenge as underlying pre-symptomatic "multisystem" disorders varying from benign to life-threatening should first be ruled out before nystagmus can be labeled as idiopathic. A multidisciplinary approach including multimodal ocular investigations and next-generation sequencing with whole-genome sequencing (WGS) or targeted gene panel testing is required to delineate the exact etiology. We report the clinical and genetic outcomes of 22 patients, from 22 unrelated families of diverse ethnicities, with IIN seen in the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between 2016 and 2022. Thirty-six percent (8/22) received a confirmed molecular diagnosis with eight mutations identified in two genes (seven in FRMD7 including one novel variant c.706_707del; p. [Lys236Alafs*66], and one in GPR143). This study expands the mutational spectrum of IIN and highlights the significant role of an integrated care pathway and broader panel testing in excluding underlying pathologies.

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.

Binocular versus standard occlusion or blurring treatment for unilateral amblyopia in children aged three to eight years.

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.

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.

Prospective Study of the Phenotypic and Mutational Spectrum of Ocular Albinism and Oculocutaneous Albinism.

Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky-Pudlak syndrome and Chédiak-Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically and genetically heterogenous (associated with seven genes). X-linked ocular albinism (OA) is associated with only one gene, GPR143. We report the clinical and genetic outcomes of 44 patients, from 40 unrelated families of diverse ethnicities, with query albinism presenting to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between November 2017 and October 2019. Thirty-six were children (≤ 16 years) with a median age of 31 months (range 2-186), and eight adults with a median age of 33 years (range 17-39); 52.3% (n = 23) were male. Genetic testing using whole genome sequencing (WGS, n = 9) or a targeted gene panel (n = 31) gave an overall diagnostic rate of 42.5% (44.4% (4/9) with WGS and 41.9% (13/31) with panel testing). Seventeen families had confirmed mutations in TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include SLC38A8-associated foveal hypoplasia and syndromic forms of albinism.

Novel Biallelic Variants and Phenotypic Features in Patients with SLC38A8-Related Foveal Hypoplasia.

Biallelic pathogenic variants in solute carrier family 38 member 8, SLC38A8, cause a pan-ocular autosomal recessive condition known as foveal hypoplasia 2, FVH2, characterised by foveal hypoplasia, nystagmus and optic nerve chiasmal misrouting. Patients are often clinically diagnosed with ocular albinism, but foveal hypoplasia can occur in several other ocular disorders. Here we describe nine patients from seven families who had molecularly confirmed biallelic recessive variants in SLC38A8 identified through whole genome sequencing or targeted gene panel testing. We identified four novel sequence variants (p.(Tyr88*), p.(Trp145*), p.(Glu233Gly) and c.632+1G>A). All patients presented with foveal hypoplasia, nystagmus and reduced visual acuity; however, one patient did not exhibit any signs of chiasmal misrouting, and three patients had features of anterior segment dysgenesis. We highlight these findings in the context of 30 other families reported to date. This study reinforces the importance of obtaining a molecular diagnosis in patients whose phenotype overlap with other inherited ocular conditions, in order to support genetic counselling, clinical prognosis and family planning. We expand the spectrum of SLC38A8 mutations which will be relevant for treatment through future genetic-based therapies.

PAX6 missense variants in two families with isolated foveal hypoplasia and nystagmus: evidence of paternal postzygotic mosaicism.

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.

The Oculome Panel Test: Next-Generation Sequencing to Diagnose a Diverse Range of Genetic Developmental Eye Disorders.

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.

Use of a Binocular Optical Coherence Tomography System to Evaluate Strabismus in Primary Position.

Importance: Current clinical methods for assessing strabismus can be prone to error. Binocular optical coherence tomography (OCT) has the potential to assess and quantify strabismus objectively and in an automated manner. Objective: To evaluate the use of a binocular OCT prototype to assess the presence and size of strabismus. Design, Setting, and Participants: Fifteen participants with strabismus were recruited in 2016 as part of the EASE study from Moorfields Eye Hospital National Health Service Foundation Trust, London, England, and 15 healthy volunteers underwent automated anterior segment imaging using the binocular OCT prototype. All participants had an orthoptic assessment, including alternating prism cover test (APCT), before undergoing imaging. Simultaneously acquired pairs of OCT images, captured with 1 eye fixating, were analyzed using ImageJ (National Institutes of Health) to assess the presence and angle of strabismus. Main Outcomes and Measures: The direction and size of strabismus measured using binocular OCT was compared with that found using APCT. Results: The median age for participants with strabismus was 55 years (interquartile range [IQR], 33-66.5 years) and for the healthy group, 50 years (IQR, 41-59 years); 15 participants (50%) were women, and 25 participants (83.3%) were white. The median magnitude of horizontal deviation was 20∆ (IQR, 13-35∆) and for vertical deviation, 3∆ (IQR, 0-5∆). Binocular OCT imaging correctly revealed the type and direction of the deviation in all 15 participants with strabismus, including horizontal and vertical deviations. The APCT and OCT measurements were strongly correlated for the horizontal (Pearson r = 0.85; 95% CI, 0.60-0.95; P < .001) and vertical (r = 0.89; 95% CI, 0.69-0.96; P < .001) deviations. In the healthy cohort, 9 of 15 participants (60%) had a latent horizontal deviation on APCT results (median magnitude 2∆, range 2-4∆). Six (40%) had orthophoria. Horizontal deviations were observed on OCT imaging results in 12 of the 15 participants (80%), and a vertical deviation was visible in 1 participant (6.7%). Conclusions and Relevance: These findings suggest that binocular anterior segment OCT imaging can provide clinicians with a precise measurement of strabismus. The prototype can potentially incorporate several binocular vision tests that will provide quantitative data for the assessment, diagnosis, and monitoring of ocular misalignments.

Functional vision and quality of life in children with microphthalmia/anophthalmia/coloboma-a cross-sectional study.

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.

Tests for detecting strabismus in children aged 1 to 6 years in the community.

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.

Binocular Therapy for Childhood Amblyopia Improves Vision Without Breaking Interocular Suppression.

Purpose: Amblyopia is a common developmental visual impairment characterized by a substantial difference in acuity between the two eyes. Current monocular treatments, which promote use of the affected eye by occluding or blurring the fellow eye, improve acuity, but are hindered by poor compliance. Recently developed binocular treatments can produce rapid gains in visual function, thought to be as a result of reduced interocular suppression. We set out to develop an effective home-based binocular treatment system for amblyopia that would engage high levels of compliance but that would also allow us to assess the role of suppression in children's response to binocular treatment. Methods: Balanced binocular viewing therapy (BBV) involves daily viewing of dichoptic movies (with "visibility" matched across the two eyes) and gameplay (to monitor compliance and suppression). Twenty-two children (3-11 years) with anisometropic (n = 7; group 1) and strabismic or combined mechanism amblyopia (group 2; n = 6 and 9, respectively) completed the study. Groups 1 and 2 were treated for a maximum of 8 or 24 weeks, respectively. Results: The treatment elicited high levels of compliance (on average, 89.4% ± 24.2% of daily dose in 68.23% ± 12.2% of days on treatment) and led to a mean improvement in acuity of 0.27 logMAR (SD 0.22) for the amblyopic eye. Importantly, acuity gains were not correlated with a reduction in suppression. Conclusions: BBV is a binocular treatment for amblyopia that can be self-administered at home (with remote monitoring), producing rapid and substantial benefits that cannot be solely mediated by a reduction in interocular suppression.

Quality of Life and Functional Vision in Children with Glaucoma.

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.

Novel molecular insights into the function and the antioxidative stress response of a Peroxiredoxin Q protein from cyanobacteria.

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 (Cp) and resolving (Cr), 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 Cp (Alr3183C46S) or Cr (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 H2O2, 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 Cr for interaction with thioredoxins and (2) demonstrates that over-expression of PrxQs can protect cyanobacteria from oxidative stresses.

Rate of Strabismus Detection on Digital Photographs Increases by Using Off-center Near Target.

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.].

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.Video abstracthttp://links.lww.com/CONR/A42.

Childhood amblyopia: current management and new trends.

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.

Saccadic vector optokinetic perimetry in children with neurodisability or isolated visual pathway lesions: observational cohort study.

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.

Binocular versus standard occlusion or blurring treatment for unilateral amblyopia in children aged three to eight years.

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.

Delivering clinical trials and observational studies in child eye health: a nationwide survey in the United Kingdom.

PURPOSE: Evidence-based medicine requires primary results from randomized controlled trials and high-quality observational studies; however, in pediatric medicine it can be difficult to enroll sufficient numbers of children to reach sample sizes required for statistical significance. The experience of clinicians and researchers with the practicalities of recruitment has not been explored, but could potentially inform best practice and lead to the development of successful research networks. Perceived barriers and facilitators to recruitment in child eye health in the United Kingdom, where adoption of trials and studies onto a central database has created a register of high quality projects, were investigated. METHODS: Studies and trials in child eye health from the United Kingdom Clinical Research Network portfolio database were identified and the named researchers contacted. Based on a validated tool, an electronic survey was created to ask about recruitment experience to identify facilitators and barriers. RESULTS: There were 46 trials and studies recruiting children, and 51 completed questionnaires from researchers were received. Children's eye research activity is mainly based at tertiary referral centers. Although most studies recruit to target, many researchers report difficulties. Availability of dedicated research teams in clinics and good communication between research team, clinical team, and families are strong facilitators. Administrative difficulties and the burden of research to clinical teams and families are strong barriers. CONCLUSIONS: Support for investigators in the form of dedicated research and administrative staff and good communication enhance recruitment to studies in child eye health.