L-DOPA is deficient in the developing albino eye, resulting in abnormalities of retinal development and visual impairment. Ongoing retinal development after birth has also been demonstrated in the developing albino eye offering a potential therapeutic window in humans. To study whether human equivalent doses of L-DOPA/Carbidopa administered during the crucial postnatal period of neuroplasticity can rescue visual function, OCA C57BL/6 J-c2J OCA1 mice were treated with a 28-day course of oral L-DOPA/Carbidopa at 3 different doses from 15 to 43 days postnatal age (PNA) and for 3 different lengths of treatment, to identify optimum dosage and treatment length.
View Article and Find Full Text PDFA guideline is proposed that comprises the minimum items to be reported in research studies involving an eye tracker and human or non-human primate participant(s). This guideline was developed over a 3-year period using a consensus-based process via an open invitation to the international eye tracking community. This guideline will be reviewed at maximum intervals of 4 years.
View Article and Find Full Text PDFBackground: Home visual acuity tests could ease pressure on ophthalmic services by facilitating remote review of patients. Home tests may have further utility in giving service users frequent updates of vision outcomes during therapy, identifying vision problems in an asymptomatic population, and engaging stakeholders in therapy.
Methods: Children attending outpatient clinics had visual acuity measured 3 times at the same appointment: Once by a registered orthoptist per clinical protocols, once by an orthoptist using a tablet-based visual acuity test (iSight Test Pro, Kay Pictures), and once by an unsupervised parent/carer using the tablet-based test.
Due to the low incidence of sixth cranial nerve palsies in children, there has been limited evidence published on this subject, especially from a population based within the UK. The incidence of etiologies has been found to vary significantly within the literature, especially with regard to neoplasms. The main aim of this study is to present the etiologies of newly diagnosed pediatric sixth nerve palsies in a UK-based population.
View Article and Find Full Text PDFNystagmus (involuntary, rhythmical eye movements) can arise due to sensory eye defects, in association with neurological disorders or as an isolated condition. We identified a family with early onset nystagmus and additional neurological features carrying a partial duplication of FGF14, a gene associated with spinocerebellar ataxia type 27 (SCA27) and episodic ataxia. Detailed eye movement analysis revealed oculomotor anomalies strikingly similar to those reported in a previously described four-generation family with early onset nystagmus and linkage to a region on chromosome 13q31.
View Article and Find Full Text PDFOculocutaneous albinism type 1 (OCA1) is caused by pathogenic variants in the TYR (tyrosinase) gene which encodes the critical and rate-limiting enzyme in melanin synthesis. It is the most common OCA subtype found in Caucasians, accounting for ~50% of cases worldwide. The apparent 'missing heritability' in OCA is well described, with ~25-30% of clinically diagnosed individuals lacking two clearly pathogenic variants.
View Article and Find Full Text PDFBosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare congenital syndrome characterized by a range of phenotypes including optic atrophy and intellectual disability among other features. Pathogenic variants in the NR2F1 (nuclear receptor subfamily 2 group F member 1) gene have been linked to this condition. A recent report has shown that pathogenic variants in the start codon lead to decreased expression of the NR2F1 protein and a relatively mild phenotype, similar to that seen in whole gene deletions, and due to the lack of the dominant negative effect.
View Article and Find Full Text PDFTher Adv Rare Dis
March 2021
Unlabelled: Nystagmus is a disorder characterised by uncontrolled, repetitive, to-and-fro movement of the eyes. It can occur as a seemingly isolated disorder but is most commonly the first, or most obvious, feature in a host of ophthalmic and systemic disorders. The number of underlying causes is vast, and recent improvements in the provision of genetic testing have shown that many conditions can include nystagmus as a feature, but that phenotypes overlap significantly.
View Article and Find Full Text PDFBackground: Electroretinograms (ERG) are necessary for the evaluation of retinal function, however testing children is challenging and only performed at a few specialised centres. The handheld RETeval ERG instrument could prove a valuable tool for clinicians in assessing retinal function. This study evaluates this device using an ISCEV approved modified paediatric protocol and compares it to standard methods using a photic stimulator.
View Article and Find Full Text PDFIn this study, we seek to exclude other pathophysiological mechanisms by which knock-down may cause Idiopathic Infantile Nystagmus (IIN) using the and murine models. We used a combination of genetic, histological and visual function techniques to characterize the role of gene in IIN using a novel murine model for the disease. We demonstrate that the allele represents a more robust model of knock-out at the mRNA level.
View Article and Find Full Text PDFNystagmus is a disorder of uncontrolled eye movement and can occur as an isolated trait (idiopathic INS, IINS) or as part of multisystem disorders such as albinism, significant visual disorders or neurological disease. Eighty-one unrelated patients with nystagmus underwent routine ocular phenotyping using commonly available phenotyping methods and were grouped into four sub-cohorts according to the level of phenotyping information gained and their findings. DNA was extracted and sequenced using a broad utility next generation sequencing (NGS) gene panel.
View Article and Find Full Text PDFCiliopathies are a clinically and genetically heterogeneous group of disorders often exhibiting phenotypic overlap and caused by abnormalities in the structure or function of cellular cilia. As such, a precise molecular diagnosis is important for guiding clinical management and genetic counseling. In the present study, two Pakistani families comprising individuals with overlapping clinical features suggestive of a ciliopathy syndrome, including intellectual disability, obesity, congenital retinal dystrophy, and hypogonadism (in males), were investigated clinically and genetically.
View Article and Find Full Text PDFPurpose: To investigate eight previously unreported Pakistani families with genetically undefined OCA for mutations in TYR.
Methods: Sanger sequencing of TYR has been performed in eight families with OCA phenotype. Mutation analysis was performed to establish the pathogenic role of novel mutation.
Pigment Cell Melanoma Res
September 2019
Albinism is a group of disorders characterized by pigment deficiency and abnormal retinal development. Despite being a common cause for visual impairment worldwide, there is a paucity of treatments and patients typically suffer lifelong visual disability. Residual plasticity of the developing retina in young children with albinism has been demonstrated, suggesting a post-natal window for therapeutic rescue.
View Article and Find Full Text PDFIntroduction: Amblyopia therapy appears to be most effective in children under the age of 7 years, but results from randomized control trials (RCTs) have shown that occlusion therapy and/or atropine penalization therapy may improve visual acuity in an older age group. Which of these two therapies is the most effective with fewer adverse effects in an older age group has not yet been agreed upon.
Methods: We systematically searched the literature for RCTs that compared atropine penalization therapy and occlusion therapy in terms of their visual acuity outcomes and adverse events and performed a meta-analysis on the visual acuity data obtained.
Background: De novo mutations in have recently been described to cause PURA syndrome, a neurodevelopmental disorder characterised by severe intellectual disability (ID), epilepsy, feeding difficulties and neonatal hypotonia.
Objectives: To delineate the clinical spectrum of PURA syndrome and study genotype-phenotype correlations.
Methods: Diagnostic or research-based exome or Sanger sequencing was performed in individuals with ID.
Oculocutaneous albinism (OCA) and ocular albinism (OA) are inherited disorders of melanin biosynthesis, resulting in loss of pigment and severe visual deficits. OCA encompasses a range of subtypes with overlapping, often hypomorphic phenotypes. OCA1 is the most common cause of albinism in European populations and is inherited through autosomal recessive mutations in the Tyrosinase (TYR) gene.
View Article and Find Full Text PDFPrevious studies have suggested that central corneal endothelial cell density (ECD) decreases from 6,100 cells/mm in neonates to 3,100 cells/mm in 10-year-olds. Currently data on ECD in young children as well as the trend for ECD decrease during childhood is sparse because of the difficulty of examination using existing clinic-based specular microscopes. We developed a novel method of imaging young children intraoperatively with the goal of beginning to establish age-specific normative data for ECD and hexagonality of cells (%HEX).
View Article and Find Full Text PDFMutations in genes involved in lipid metabolism have increasingly been associated with various subtypes of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative motor neuron disorders characterized by spastic paraparesis. Here, we report an unusual autosomal recessive neurodegenerative condition, best classified as a complicated form of hereditary spastic paraplegia, associated with mutation in the ethanolaminephosphotransferase 1 (EPT1) gene (now known as SELENOI), responsible for the final step in Kennedy pathway forming phosphatidylethanolamine from CDP-ethanolamine. Phosphatidylethanolamine is a glycerophospholipid that, together with phosphatidylcholine, constitutes more than half of the total phospholipids in eukaryotic cell membranes.
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