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Item does not contain fulltext, This study describes the clinical spectrum and genetic background of high myopia caused by mutations in the ARR3 gene. We performed an observational case series of three multigenerational families with high myopia (SER≤-6D), from the departments of Clinical Genetics and Ophthalmology of a tertiary Dutch hospital. Whole-exome sequencing (WES) with a vision-related gene panel was performed, followed by a full open exome sequencing. We identified three Caucasian families with high myopia caused by three different pathogenic variants in the ARR3 gene (c.214C>T, p.Arg72*; c.767+1G>A; p.?; c.848delG, p.(Gly283fs)). Myopia was characterized by a high severity (<-8D), an early onset (<6 years), progressive nature, and a moderate to bad atropine treatment response. Remarkably, a female limited inheritance pattern was present in all three families accordant with previous reports. The frequency of a pathogenic variant in the ARR3 gene in our diagnostic WES cohort was 5%. To conclude, we identified three families with early onset, therapy-resistant, high myopia with a female-limited inheritance pattern, caused by a mutation in the ARR3 gene. The singular mode of inheritance might be explained by metabolic interference due to X-inactivation. Identification of this type of high myopia will improve prompt myopia treatment, monitoring, and genetic counseling.

Item does not contain fulltext, High myopia [refractive error ≤ -6 diopters (D)] is a heterogeneous condition, and without clear accompanying features, it can be difficult to pinpoint a genetic cause. This observational study aimed to evaluate the utility of whole exome sequencing (WES) using an eye disorder gene panel in European patients with high myopia. Patients with high myopia were recruited by ophthalmologists and clinical geneticists. Clinical features were categorized into isolated high myopia, high myopia with other ocular involvement or with systemic involvement. WES was performed and an eye disorder gene panel of ~500 genes was evaluated. Hundred and thirteen patients with high myopia [mean (SD) refractive error - 11.8D (5.2)] were included. Of these, 53% were children younger than 12 years of age (53%), 13.3% were aged 12-18 years and 34% were adults (aged > 18 years). Twenty-three out of 113 patients (20%) received a genetic diagnosis of which 11 patients displayed additional ocular or systemic involvement. Pathogenic variants were identified in retinal dystrophy genes (e.g. GUCY2D and CACNA1F), connective tissue disease genes (e.g. COL18A1 and COL2A1), non-syndromic high myopia genes (ARR3), ocular development genes (e.g. PAX6) and other genes (ASPH and CNNM4). In 20% of our high myopic study population, WES using an eye gene panel enabled us to diagnose the genetic cause for this disorder. Eye genes known to cause retinal dystrophy, developmental or syndromic disorders can cause high myopia without apparent clinical features of other pathology.

Contains fulltext : 229723.pdf (Publisher’s version ) (Open Access), BACKGROUND: Atropine is the most powerful treatment for progressive myopia in childhood. This study explores the 3-year effectiveness of atropine in a clinical setting. METHODS: In this prospective clinical effectiveness study, children with progressive myopia ≥ 1D/year or myopia ≤ -2.5D were prescribed atropine 0.5%. Examination, including cycloplegic refraction and axial length (AL), was performed at baseline, and follow-up. Outcome measures were spherical equivalent (SER) and AL; annual progression of SER on treatment was compared with that prior to treatment. Adjustments to the dose were made after 1 year in case of low (AL ≥ 0.3 mm/year) or high response (AL < 0.1 mm/year) of AL. RESULTS: A total of 124 patients were enrolled in the study (median age: 9.5, range: 5-16 years). At baseline, median SER was -5.03D (interquartile range (IQR): 3.08); median AL was 25.14 mm (IQR: 1.30). N = 89 (71.8%) children were persistent to therapy throughout the 3-year follow-up. Median annual progression of SER for these children was -0.25D (IQR: 0.44); of AL 0.11 mm (IQR: 0.18). Of these, N = 32 (36.0%) had insufficient response and were assigned to atropine 1%; N = 26 (29.2%) showed good response and underwent tapering in dose. Rebound of AL progression was not observed. Of the children who ceased therapy, N = 9 were lost to follow-up; N = 9 developed an allergic reaction; and N = 17 (19.1%) stopped due to adverse events. CONCLUSION: In children with or at risk of developing high myopia, a starting dose of atropine 0.5% was associated with decreased progression in European children during a 3-year treatment regimen. Our study supports high-dose atropine as a treatment option for children at risk of developing high myopia in adulthood.

Ocular anomalies may occur in craniofacial microsomia (CFM). The aim of this systematic review was to review the literature on ocular anomalies and their incidence, in order to estimate the need for ophthalmological screening in CFM patients. Online databases were searched, and data on the number of patients, type and incidence of ocular anomalies, and visual acuity were extracted. Four subgroups of ocular and adnexal anomalies were identified, to provide an overview of the different anomalies. Twenty-five papers analysing 1419 patients in total were included. Ocular anomalies were documented in 6.7–100% of patients. The most reported type I ocular anomalies were eyelid coloboma, lipodermoids, and orbital dystopia. The most reported type II ocular anomalies were epibulbar dermoid, microphthalmia, and anophthalmia. Ptosis a

Purpose: To determine change in visual acuity (VA) in the population of a previous amblyopia treatment study (Loudon 2006) and assess risk factors for VA decrease. Methods: Subjects treated between 2001 and 2003 were contacted between December 2015 and July 2017. Orthoptic examination was conducted under controlled circumstances and included subjective refraction, best corrected VA, reading acuity, binocular vision, retinal fixation, cover-uncover and alternating cover test. As a measure for degree of amblyopia, InterOcular VA Difference (IOD) at the end of occlusion therapy was compared with IOD at the follow-up examination using Wilcoxon’s signed-rank test. Regression analysis was conducted to determine the influence of clinical and socio-economic factors on changes in IOD. Results: Out of 303 subjects from the original study, 208 were contacted successfully, 59 refused and 15 were excluded because of non-amblyopic cause of visual impairment. Mean IOD at end of therapy (mean age 6.4 years) was 0.11 ± 0.16 logMAR, and IOD at follow-up examination (mean age 18.3 years) was 0.09 ± 0.21 logMAR; this difference was not significant (p = 0.054). Degree of anisometropia (p = 0.008; univariable analysis), increasing anisometropia (p = 0.009; multivariable), eccentric fixation (p < 0.001; univariable and multivariable); large IOD (p < 0.001; univariable and multivariable) and non-compliance during therapy (p = 0.028; univariable) were associated with IOD increase. Conclusion: Long-term results of occlusion therapy were good. High or increasing anisometropia, eccentric fixation and non-compliance during occlusion therapy were associated with long-term VA decrease. Subjects with poor initial VA had a larger increase despite little patching, but often showed long-term VA decrease.

BACKGROUND: An increasing number of children are suffering from brain damage-related visual processing dysfunctions (VPD). There is currently a lack of evidence-based intervention methods that can be used early in development. We developed a visual intervention protocol suitable from 1 year of age. The protocol is structured, comprehensive and individually adaptive, and is paired with quantitative outcome assessments. Our aim is to investigate the effectiveness of this first visual intervention program for young children with (a risk of) VPD. METHODS: This is a single-blind, placebo-controlled trial that is embedded within standard clinical care. The study population consists of 100 children born very or extremely preterm (< 30 weeks) at 1 year of corrected age (CA), of whom 50% are expected to have VPD. First, children undergo a visual screening at 1 year CA. If they are classified as being at risk of VPD, they are referred to standard care, which involves an ophthalmic and visual function assessment and a (newly developed) visual intervention program. This program consists of a general protocol (standardized and similar for all children) and a supplement protocol (adapted to the specific needs of the child). Children are randomly allocated to an intervention group (starting upon inclusion at 1 year CA) or a control group (postponed: starting at 2 years CA). The control group will receive a placebo treatment. The effectiveness of early visual intervention will be examined with follow-up visual and neurocognitive assessments after 1 year (upon completion of the direct intervention) and after 2 years (upon completion of the postponed intervention). DISCUSSION: Through this randomized controlled trial we will establish the effectiveness of a new and early

Background: Children with Apert and Crouzon-Pfeiffer syndromes are at risk of intracranial hypertension. Until 2005, when the authors switched to occipital expansion, their institution's preferred treatment was fronto-orbital advancement. However, it was still unclear whether (1) occipitofrontal head circumference (i.e., intracranial volume) was greater after occipital expansion than after fronto-orbital advancement; (2) the incidences of tonsillar herniation and papilledema were lower; and (3) visual acuity was better during follow-up. In these patients, the authors therefore compared fronto-orbital advancement with occipital expansion as the first surgical procedure. Methods: Measurements included repeated occipitofrontal head circumference as a measure for intracranial volume; neuroimaging to evaluate tonsillar herniation; funduscopy to identify papilledema; and visual acuity testing. Results: The authors included 37 patients (Apert syndrome, n = 18; Crouzon-Pfeiffer syndrome, n = 19). Eighteen underwent fronto-orbital advancement and 19 underwent occipital expansion (age at surgery, 1.0 versus 1.5 years; p = 0.13). Follow-up time in both groups was 5.7 years. The increase in occipitofrontal head circumference (+1.09 SD) was greater after occipital expansion than after fronto-orbital advancement (+0.32 SD) (p = 0.03). After occipital expansion, fewer patients with Crouzon-Pfeiffer syndrome had tonsillar herniation (occipital, three of 11; fronto-orbital advancement, seven of eight; p = 0.02); for both syndromes together, fewer patients had papilledema (occipital, four of 19; fronto-orbital advancement, 11 of 18; p = 0.02). Visual acuity was similar after fronto-orbital advancement and occipital expansion (0.09 versus 0.13 logarithm of the minimum angle of resolution) (p = 0.28). Conclusions: The authors' preference for occipital expansion as the initial craniofacial procedure in Apert and Crouzon-Pfeiffer syndromes is supported by the greater increase it produces

Background: Compliance with occlusion therapy for amblyopia in children is low when their parents have a low level of education, speak Dutch poorly, or originate from another country. We determined how sociocultural and psychological determinants affect compliance. Methods: Included wer

Purpose. The Pediatric Vision Scanner (PVS) detects strabismus by identifying ocular fixation in both eyes simultaneously. This study was undertaken to assess the ability of the PVS to identify patients with amblyopia or strabismus, particularly anisometropic amblyopia with no measurable strabismus. Methods. The PVS test, administered from 40 cm and requiring 2.5 seconds of attention, generated a binocularity score (BIN, 0%-100%). We tested 154 patients and 48 controls between the ages of 2 and 18 years. BIN scores of amblyopic children and controls were measured, and 21 children received sequential PVS measurements to detect any changes in BIN resulting from amblyopia treatment. Results. With the pass/refer threshold set at BIN 60%, sensitivity and specificity were 96% for the detection of amblyopia or strabismus. Assuming a 5% prevalence of amblyopia or strabismus, the inferred positive and negative predictive values of the PVS were 56% and 100%, respectively. Fixation accuracy was significantly reduced in amblyopic ey

The term ‘amblyopia’ originates from the Greek language and literally means dimness or dullness of vision. In time, the condition has been defined in a variety of ways, very much depending on the prevailing patho-physiological concept about its etiology. In general, amblyopia can be defined as a unilateral or bilateral decrease in visual acuity for which no organic cause can be found on physical examination of the eye. It is caused by a refractive error (one foveal image is more blurred than the other); strabismus (ocular misalignment causing each eye to have a different image on the fovea) or, more rarely, deprivation of a clear retinal image (physical obstruction, e.g. infantile cataract, ptosis) (von Noorden 1967; 1985; von Noorden and Campos 2002). Amblyopia usually presents itself during the ophthalmological examination by the ophthalmologist or the orthoptist as a reduced visual acuity in one or both eyes, in the presence of a re

PURPOSE. Noncompliance is one of the limiting factors in the success of occlusion therapy for amblyopia. Electronic monitoring was used to investigate predictors of noncompliance, and, in a prospective randomized clinical trial, determined the effectiveness of an educational program. METHODS. Compliance was measured electronically during 1 week every 3 months in 310 newly diagnosed amblyopic children. The family's demographic parameters and the child's clinical parameters were assessed for their influence on the level of compliance. In addition to standard orthoptic care, children were randomized to receive an educational cartoon story, reward stickers, and an information sheet for the parents (intervention group), or a picture to color (reference group). These and the electronic device were distributed during home visits by researchers. The primary outcome measure was the percentage of compliance (actual/prescribed occlusion time) in the two groups. The secondary outcome measure was the influence of demographic and clinical factors on compliance. RESULTS. Compliance was associated with parental fluency in the national language, country of origin, level of education, and initial visual acuity of the child. During the first 1-week measurement period children in the intervention group had better compliance than the reference group had (78% ± 32% vs. 57% ± 40%; P < 0.0001), and fewer children were not occluded at all (3 vs. 23 in the reference group; P < 0.0001). This difference remained throughout the study period. CONCLUSIONS. Poor parental fluency in the national language, a low level of education, and poor acuity at the start of treatment were predictors of low compliance. An educational program primarily aimed at the child improved compliance and reduced the number of children who did not comply with occlusion at all. Copyright