Myopia Management

Myopia is already the most common ocular disorder in the world, and its prevalence continues to increase worldwide. Higher myopic refractive errors are associated with an increased risk of vision-threatening complications, which has led to many investigations into the underlying cause of myopia and the mechanisms of myopia progression in order to prevent or delay the onset of myopia and slow its progression. This chapter briefly reviews ocular development and emmetropization, summarizes the known risk factors for myopia onset and myopia progression, reviews current clinical interventions for controlling myopia, and provides practice management recommendations. Finally, instances of syndromic myopia, which have not been shown to be responsive to myopia control treatments, are reviewed.

Jack of all trades, master of each: the diversity of fibroblast growth factor signalling in eye development

A central question in development biology is how a limited set of signalling pathways can instruct unlimited diversity of multicellular organisms. In this review, we use three ocular tissues as models of increasing complexity to present the astounding versatility of fibroblast growth factor (FGF) signalling. In the lacrimal gland, we highlight the specificity of FGF signalling in a one-dimensional model of budding morphogenesis. In the lens, we showcase the dynamics of FGF signalling in altering functional outcomes in a two-dimensional space. In the retina, we present the prolific utilization of FGF signalling from three-dimensional development to homeostasis. These examples not only shed light on the cellular basis for the perfection and complexity of ocular development, but also serve as paradigms for the diversity of FGF signalling.

Novel BMP4 Truncations Resulted in Opposite Ocular Anomalies: Pathologic Myopia Rather Than Microphthalmia

BMP4 variants have been reported to be associated with syndromic microphthalmia (MCOPS6, OMIM 607932). This study aims to describe BMP4 truncation mutations contributing to a novel phenotype in eight patients from four Chinese families. In this study, BMP4 variants were collected from a large dataset from in-house exome sequencing. Candidate variants were filtered by multiple in silico tools as well as comparison with data from multiple databases. Potential pathogenic variants were further confirmed by Sanger sequencing and cosegregation analysis. Four novel truncation variants in BMP4 were detected in four out of 7,314 unrelated probands with different eye conditions. These four mutations in the four families solely cosegregated in all eight patients with a specific form of pathologic myopia, characterized by significantly extended axial length, posterior staphyloma, macula patchy, chorioretinal atrophy, myopic optic neuropathy or glaucoma, vitreous opacity, and unique peripheral snow-grain retinopathy. The extreme rarity of the truncations in BMP4 (classified as intolerant in the gnomAD database, pLI = 0.96), the exclusive presence of these variants in the four families with pathologic myopia, variants fully co-segregated with the same specific phenotypes in eight patients from the four families, and the association of the pathogenicity of truncations with syndromic microphthalmia in previous studies, all support a novel association of BMP4 truncations with a specific form of pathologic myopia. The data presented in this study demonstrated that heterozygous BMP4 truncations contributed to a novel phenotype: pathologic myopia rather than microphthalmia. Mutations in the same gene resulting in both high myopia and microphthalmia have been observed for a few other genes like FZD5 and PAX6, suggesting bidirectional roles of these genes in early ocular development. Further studies are expected to elucidate the molecular mechanism of the bidirectional regulation.

Analysis of BMP3 Variants In The Causality of Ocular Coloboma

Coloboma, a congenital disorder characterized by gaps in ocular tissues, is caused when the choroid fissure fails to close during embryonic development. Several loci have been associated with coloboma, but these represent less than 40% of those that are involved with this disease. Here, we describe a novel coloboma-causing locus, BMP3. Whole exome sequencing and Sanger sequencing of patients with coloboma identified three variants in BMP3, two of which are predicted to be disease causing. Consistent with this, bmp3 mutant zebrafish have aberrant fissure closure. bmp3 is expressed in the ventral head mesenchyme and regulates phosphorylated Smad3 in a population of cells adjacent to the choroid fissure. Furthermore, mutations in bmp3 sensitize embryos to Smad3 inhibitor treatment resulting in open choroid fissures. Micro CT scans and Alcian blue staining of zebrafish demonstrate that mutations in bmp3 cause midface hypoplasia, suggesting that bmp3 regulates cranial neural crest cells. Consistent with this, we see active Smad3 in a population of periocular neural crest cells, and bmp3 mutant zebrafish have reduced neural crest cells in the choroid fissure. Taken together, this data suggests that Bmp3 controls Smad3 phosphorylation in neural crest cells to regulate early craniofacial and ocular development.

Analysis of BMP3 variants in the causality of ocular coloboma

Coloboma, a congenital disorder characterized by gaps in ocular tissues, is caused when the choroid fissure fails to close during embryonic development. Several loci have been associated with coloboma, but these represent less than 40% of those that are involved with this disease. Here, we describe a novel coloboma-causing locus, BMP3. Whole exome sequencing and Sanger sequencing of patients with coloboma identified three variants in BMP3, two of which are predicted to be disease causing. Consistent with this, bmp3 mutant zebrafish have aberrant fissure closure. bmp3 is expressed in the ventral head mesenchyme and regulates phosphorylated Smad3 in a population of cells adjacent to the choroid fissure. Furthermore, mutations in bmp3 sensitize embryos to Smad3 inhibitor treatment resulting in open choroid fissures. Micro CT scans and Alcian blue staining of zebrafish demonstrate that mutations in bmp3 cause midface hypoplasia, suggesting that bmp3 regulates cranial neural crest cells. Consistent with this, we see active Smad3 in a population of periocular neural crest cells, and bmp3 mutant zebrafish have reduced neural crest cells in the choroid fissure. Taken together, this data suggests that Bmp3 controls Smad3 phosphorylation in neural crest cells to regulate early craniofacial and ocular development.

Two Cases of Ocular Manifestations in Patients with Microdeletion of the Chromosome 7 Long Arm

Purpose: We report ocular manifestations in two patients with 7q microdeletion. Case summary: (Case 1) A 62-day-old male infant was admitted to the ophthalmology outpatient department for ocular examination after being diagnosed with microdeletion of chromosome seven (7q36.2q36.3 deletion) in DNA microarray comparative genomic hybridization (DNA microarray CGH) and fluorescence in situ hybridization (FISH) tests. Fundus examination showed optic disc hypoplasia in both eyes and retinopathy of prematurity, accompanied by retinal hemorrhage in his right eye. Around the age of 24 months, the patient was diagnosed with intermittent exotropia with anisometropia and was prescribed spectacles. (Case 2) A 3-year-old male infant was referred to the ophthalmology clinic to evaluate poor fixation, which was found during rehabilitation therapy for cerebral palsy and developmental delay. Fundus examination showed an increased cup/disc ratio bilaterally. A flash visual evoked potential test indicated a decrease in amplitude in his right eye. Intermittent exotropia of forty prism diopters was observed. DNA microarray CGH and FISH tests performed at another hospital revealed microdeletion of chromosome seven (7q35 microdeletion) and CNTNAP2 gene loss. Conclusions: When genetic anomalies associated with ocular development are identified, it is necessary to detect the ophthalmic abnormalities early and provide the appropriate treatment to allow for the development of normal visual function.

Lineage Contribution of PDGFRα-Expressing Cells in the Developing Mouse Eye

PDGFRα signaling is critically important in ocular development. Previous data on PDGFRα lacks an expression map with high spatial and temporal resolution and lineage information. In this study, we aim to present a detailed PDGFRα expression and lineage map from early embryogenesis to adulthood. PDGFRα-CreER; mT/mG reporter mice were analyzed. mEGFP-positive cells contributed to multiple ocular lineages in a spatiotemporally regulated manner. A dynamic PDGFRα expression was identified in corneal stromal cells, lens epithelial cells, lens fiber cells, and retinal astrocytes during the entire period of eye development, while PDGFRα expression in retinal astrocytes from E17.5 onwards and in Müller glial cells was identified within two weeks after birth. By revealing detailed characterization of gene expression and function, we present a comprehensive map of PDGFRα-expressing cells in the eye for a better understanding of PDGFRα signaling’s role during eye development.

Fundamentos para a prática clínica na terapia ocupacional: a visão de lactentes em foco/ Fundamentals for clinical practice in Occupational Therapy: the view of infants in focus

A atuação do terapeuta ocupacional no campo da saúde ocular e visual para a promoção do desenvolvimento infantil e prevenção de deficiências, requer conhecimento amplo e sólido sobre a complexidade da fundamentação teórica que norteia e sustenta a prática clínica. Ao mesmo tempo, necessita de um olhar individualizado para as potências, comportamentos e características de cada criança, especialmente nos primeiros anos de vida. O presente editorial busca contextualizar conceitos fundamentais sobre processos de plasticidade e maturação neurológica, desenvolvimento ocular e de funções visuais/visuomotoras, relacionar saberes da saúde e educação com níveis de prevenção com base no conhecimento científico. Objetiva minimizar divergências teóricas e conceituais no campo em questão e oferecer suporte teórico para a clínica de terapeutas ocupacionais no processo de intervenção oportuna e habilitação visual de bebês e crianças com diagnóstico ou em risco para alterações no desenvolvimento da visão, a fim de potencializar experiências para a máxima expressão do desenvolvimento infantil.Palavras-chave: Terapia Ocupacional. Saúde Ocular. Prevenção de Doenças. AbstractThe work of the occupational therapist in the field of eye and visual health to promote child development and prevent disabilities requires broad and solid knowledge about the complexity of the theoretical foundation that guides and sustains clinical practice. At the same time, it needs an individualized look at the powers, behaviors and characteristics of each child, especially in the first years of life. This editorial seeks to contextualize fundamental concepts about processes of neurological plasticity and maturation, ocular development and visual/ visomotor functions and to relate health and education knowledge to prevention levels based on scientific knowledge. It aims to minimize theoretical and conceptual divergences in the field in question, and offer theoretical support to the clinic of occupational therapists in the process of timely intervention and visual enabling of babies and children diagnosed or at risk for changes in vision development, in order to enhance experiences for the maximum expression of child development. Keywords: Occupational Therapy; Eye Health; Disease Prevention.ResumenEl rol del terapeuta ocupacional en el campo de la salud ocular y visual para promover el desarrollo infantil y prevenir discapacidades requiere un conocimiento amplio y sólido sobre la complejidad del fundamento teórico que guía y sustenta la práctica clínica. Al mismo tiempo, necesita una mirada individualizada a los poderes, comportamientos y características de cada niño, especialmente en los primeros años de vida. Este editorial busca contextualizar conceptos fundamentales sobre plasticidad y procesos de maduración neurológica, desarrollo ocular y funciones visuales / visuomotoras y relacionar el conocimiento en salud y educación con niveles de prevención basados en el conocimiento científico. Tiene como objetivo minimizar las divergencias teóricas y conceptuales en el campo en cuestión, y ofrecer apoyo teórico a la clínica de terapeutas ocupacionales en el proceso de intervención oportuna y habilitación visual de bebés y niños diagnosticados o en riesgo de cambios en el desarrollo de la visión, con el fin de potenciar las experiencias para la máxima expresión del desarrollo infantil.Palabras clave: Terapia Ocupacional. Salud Ocular. Prevención de Enfermedades.

E3 ubiquitin ligase-mediated regulation of vertebrate ocular development; new insights into the function of SIAH enzymes

Developmental regulation of the vertebrate visual system has been a focus of investigation for generations as understanding this critical time period has direct implications on our understanding of congenital blinding disease. The majority of studies to date have focused on transcriptional regulation mediated by morphogen gradients and signaling pathways. However, recent studies of post translational regulation during ocular development have shed light on the role of the ubiquitin proteasome system (UPS). This rather ubiquitous yet highly diverse system is well known for regulating protein function and localization as well as stability via targeting for degradation by the 26S proteasome. Work from many model organisms has recently identified UPS activity during various milestones of ocular development including retinal morphogenesis, retinal ganglion cell function as well as photoreceptor homeostasis. In particular work from flies and zebrafish has highlighted the role of the E3 ligase enzyme family, Seven in Absentia Homologue (Siah) during these events. In this review, we summarize the current understanding of UPS activity during Drosophila and vertebrate ocular development, with a major focus on recent findings correlating Siah E3 ligase activity with two major developmental stages of vertebrate ocular development, retinal morphogenesis and photoreceptor specification and survival.