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Eye (London, England) Jan 2015Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis. Cases can be autosomal dominant, autosomal recessive, or X-linked. FEVR... (Review)
Review
Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis. Cases can be autosomal dominant, autosomal recessive, or X-linked. FEVR patients have an avascular peripheral retina which, depending on the degree of ischaemia, causes the secondary complications of the disease. Expressivity may be asymmetric and is highly variable. Five genes have been identified that when mutated, cause FEVR; NDP (X-linked), FZD4 (autosomal dominant and recessive), LRP5 (autosomal dominant and recessive), TSPAN12 (autosomal dominant and recessive), and ZNF408 (autosomal dominant). Four of these genes have been shown to have a central role in Norrin/Frizzled4 signalling, suggesting a critical role for this pathway in retinal angiogenesis. In addition to the ocular features, LRP5 mutations can cause osteopenia and osteoporosis. All FEVR patients in whom molecular testing is not easily accessible should have dual energy X-ray absorptiometry (DEXA) scans to assess bone mineral density, as treatment can be initiated to reduce the risk of bone fractures.
Topics: DNA-Binding Proteins; Eye Diseases, Hereditary; Eye Proteins; Familial Exudative Vitreoretinopathies; Frizzled Receptors; Humans; Low Density Lipoprotein Receptor-Related Protein-5; Mutation; Nerve Tissue Proteins; Retinal Diseases; Tetraspanins; Transcription Factors; Vitreoretinopathy, Proliferative
PubMed: 25323851
DOI: 10.1038/eye.2014.70 -
Archives of Disease in Childhood Sep 2017An estimated 1.4 million of the world's children are blind. A blind child is more likely to live in socioeconomic deprivation, to be more frequently hospitalised during... (Review)
Review
An estimated 1.4 million of the world's children are blind. A blind child is more likely to live in socioeconomic deprivation, to be more frequently hospitalised during childhood and to die in childhood than a child not living with blindness. This update of a previous review on childhood visual impairment focuses on emerging therapies for children with severe visual disability (severe visual impairment and blindness or SVI/BL).For children in higher income countries, cerebral visual impairment and optic nerve anomalies remain the most common causes of SVI/BL, while retinopathy of prematurity (ROP) and cataract are now the most common avoidable causes. The constellation of causes of childhood blindness in lower income settings is shifting from infective and nutritional corneal opacities and congenital anomalies to more resemble the patterns seen in higher income settings. Improvements in maternal and neonatal health and investment in and maintenance of national ophthalmic care infrastructure are the key to reducing the burden of avoidable blindness. New therapeutic targets are emerging for childhood visual disorders, although the safety and efficacy of novel therapies for diseases such as ROP or retinal dystrophies are not yet clear. Population-based epidemiological research, particularly on cerebral visual impairment and optic nerve hypoplasia, is needed in order to improve understanding of risk factors and to inform and support the development of novel therapies for disorders currently considered 'untreatable'.
Topics: Blindness; Cataract; Child; Corneal Opacity; Eye Diseases, Hereditary; Global Health; Humans; Income; Infant, Newborn; Optic Nerve; Prevalence; Retinal Diseases; Retinopathy of Prematurity
PubMed: 28465303
DOI: 10.1136/archdischild-2016-310532 -
Cornea May 2019Sjögren's syndrome (SS) is a common autoimmune disease affecting about four million Americans. Although approximately 1 in 10 patients with clinically-significant... (Review)
Review
PURPOSE
Sjögren's syndrome (SS) is a common autoimmune disease affecting about four million Americans. Although approximately 1 in 10 patients with clinically-significant aqueous deficient dry eye has underlying SS, widespread underappreciation of SS leads to significant underdiagnosis, delays in diagnosis, and consequent morbidity and mortality. The purpose of this article is to illustrate that in addition to dry eye, SS can cause serious, vision-threatening extraglandular ocular manifestations.
METHODS
We conducted a narrative review of studies that have examined the dry eye and extraglandular ocular complications of SS.
RESULTS
SS-related dry eye is a progressive condition with major negative impact on the quality-of-life of afflicted patients, not only due to symptoms of ocular discomfort but also visual dysfunction. In addition, SS can lead to corneal melt/perforation, uveitis, scleritis, retinal vasculitis, and optic neuritis. A major problem with currently-available SS disease activity measurement instruments is the lack of domains evaluating dry eye-related visual dysfunction. For example, one of the most commonly-used instruments for assessing patient symptoms in SS (the EULAR Sjögren's Syndrome Patient Reported Index [ESSPRI]) only includes one item (out of three) that addresses the severity of overall dryness, without mention of dry eye symptoms or vision-related quality-of-life. Similarly, no extraglandular ocular complications are included in currently-available SS disease activity instruments (e.g., the EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]).
CONCLUSIONS
There needs to be a paradigm shift in which eye care providers and rheumatologists become more familiar with various SS-related extraglandular ocular manifestations. Existing disease activity measurement instruments must incorporate dry eye symptoms, particularly those related to visual dysfunction. An evidence-based screening algorithm for determining which patients with dry eye should be tested for underlying SS may be particularly helpful in preventing delays in diagnosis.
Topics: Dry Eye Syndromes; Eye Diseases; Humans; Quality of Life; Sjogren's Syndrome; Vision Disorders
PubMed: 30681523
DOI: 10.1097/ICO.0000000000001865 -
Molecular Vision 2021Rosacea is a chronic inflammatory disease that affects the face skin. It is clinically classified into the following four subgroups depending on its location and... (Review)
Review
Rosacea is a chronic inflammatory disease that affects the face skin. It is clinically classified into the following four subgroups depending on its location and severity: erythematotelangiectatic, papulopustular, phymatous, and ocular. Rosacea is a multifactorial disease triggered by favoring factors, the pathogenesis of which remains imperfectly understood. Recognized mechanisms include the innate immune system, with the implication of Toll-like receptors (TLRs) and cathelicidins; neurovascular deregulation involving vascular endothelial growth factor (VEGF), transient receptor potential (TRP) ion channels, and neuropeptides; and dysfunction of skin sebaceous glands and ocular meibomian glands. Microorganisms, genetic predisposition, corticosteroid treatment, and ultraviolet B (UVB) radiation are favoring factors. In this paper, we review the common and specific molecular mechanisms involved in the pathogenesis of cutaneous and ocular rosacea and discuss laboratory and clinical studies, as well as experimental models.
Topics: Animals; Disease Models, Animal; Eye Diseases; Humans; Models, Biological; Rosacea; Skin Diseases
PubMed: 34035646
DOI: No ID Found -
Expert Review of Gastroenterology &... Apr 2019Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently... (Review)
Review
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently observed and involve the joints, eyes, hepatobiliary tract, and skin. Areas covered: In this review, we discuss classical EIM focusing on epidemiology, genetics, and pathogenesis, highlighting recent advances in the understanding of EIM. We further discuss treatment-induced immunological phenomena, which are increasingly recognized and might challenge IBD-treating physicians in the era of biological treatment. Expert opinion: EIM considerably contributes to morbidity and mortality. Genetic studies have revealed a common genetic background between EIM and IBD and among specific EIM. Identified protein interactions have been shown to cluster in shared biological pathways. However - despite these recent advances - pathogenesis of EIM is at best partially understood. Several pathogenic mechanisms have been proposed such as upregulation of tumor necrosis factor, aberrant lymphocyte homing, and cross-reactive antigen presentation. It still remains unclear whether EIM is a direct result of the inflammatory process in the gut or rather a consequence of a shared genetic background leading to dysfunctional immune responses to environmental stimuli. Exploration and understanding of EIM genetics and pathophysiology will pave the road for better and more efficacious treatment options in the future.
Topics: Digestive System Diseases; Eye Diseases; Genetic Predisposition to Disease; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Joint Diseases; Phenotype; Prognosis; Risk Assessment; Risk Factors; Skin Diseases
PubMed: 30791773
DOI: 10.1080/17474124.2019.1574569 -
International Journal of Molecular... Jan 2022Oxidative stress is an important pathomechanism found in numerous ocular degenerative diseases. To provide a better understanding of the mechanism and treatment of... (Review)
Review
Oxidative stress is an important pathomechanism found in numerous ocular degenerative diseases. To provide a better understanding of the mechanism and treatment of oxidant/antioxidant imbalance-induced ocular diseases, this article summarizes and provides updates on the relevant research. We review the oxidative damage (e.g., lipid peroxidation, DNA lesions, autophagy, and apoptosis) that occurs in different areas of the eye (e.g., cornea, anterior chamber, lens, retina, and optic nerve). We then introduce the antioxidant mechanisms present in the eye, as well as the ocular diseases that occur as a result of antioxidant imbalances (e.g., keratoconus, cataracts, age-related macular degeneration, and glaucoma), the relevant antioxidant biomarkers, and the potential of predictive diagnostics. Finally, we discuss natural antioxidant therapies for oxidative stress-related ocular diseases.
Topics: Antioxidants; Biomarkers; Cataract; Eye; Eye Diseases; Glaucoma; Humans; Lens, Crystalline; Macular Degeneration; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species
PubMed: 35163178
DOI: 10.3390/ijms23031255 -
Annual Review of Vision Science Sep 2019Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or... (Review)
Review
Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or disruption of the lens microarchitecture. In general, genes involved in inherited cataracts reflect important processes and pathways in the lens including lens crystallins, connexins, growth factors, membrane proteins, intermediate filament proteins, and chaperones. Usually, mutations causing severe damage to proteins cause congenital cataracts, while milder variants increasing susceptibility to environmental insults are associated with age-related cataracts. These may have different pathogenic mechanisms: Congenital cataracts induce the unfolded protein response and apoptosis. By contrast, denatured crystallins in age-related cataracts are bound by α-crystallin and form light-scattering HMW aggregates. New therapeutic approaches to age-related cataracts use chemical chaperones to solubilize HMW aggregates, while attempts are being made to regenerate lenses using endogenous stem cells to treat congenital cataracts.
Topics: Apoptosis; Cataract; Crystallins; Eye Diseases, Hereditary; Humans; Stem Cell Transplantation
PubMed: 31525139
DOI: 10.1146/annurev-vision-091517-034346 -
Progress in Retinal and Eye Research Mar 2023Myopia is the most common eye disorder, caused by heterogeneous genetic and environmental factors. Rare progressive and stationary inherited retinal disorders are often... (Meta-Analysis)
Meta-Analysis Review
Myopia is the most common eye disorder, caused by heterogeneous genetic and environmental factors. Rare progressive and stationary inherited retinal disorders are often associated with high myopia. Genes implicated in myopia encode proteins involved in a variety of biological processes including eye morphogenesis, extracellular matrix organization, visual perception, circadian rhythms, and retinal signaling. Differentially expressed genes (DEGs) identified in animal models mimicking myopia are helpful in suggesting candidate genes implicated in human myopia. Complete congenital stationary night blindness (cCSNB) in humans and animal models represents an ON-bipolar cell signal transmission defect and is also associated with high myopia. Thus, it represents also an interesting model to identify myopia-related genes, as well as disease mechanisms. While the origin of night blindness is molecularly well established, further research is needed to elucidate the mechanisms of myopia development in subjects with cCSNB. Using whole transcriptome analysis on three different mouse models of cCSNB (in Gpr179, Lrit3 and Grm6), we identified novel actors of the retinal signaling cascade, which are also novel candidate genes for myopia. Meta-analysis of our transcriptomic data with published transcriptomic databases and genome-wide association studies from myopia cases led us to propose new biological/cellular processes/mechanisms potentially at the origin of myopia in cCSNB subjects. The results provide a foundation to guide the development of pharmacological myopia therapies.
Topics: Animals; Mice; Humans; Night Blindness; Genome-Wide Association Study; Electroretinography; Mutation; Eye Diseases, Hereditary; Genetic Diseases, X-Linked; Myopia; Membrane Proteins
PubMed: 36669906
DOI: 10.1016/j.preteyeres.2022.101155 -
Clinics in Chest Medicine Dec 2015Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues and may cause uveitis,... (Review)
Review
Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement, and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multidisciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations.
Topics: Eye Diseases; Humans; Inflammation; Optic Nerve Diseases; Sarcoidosis; Uveitis
PubMed: 26593141
DOI: 10.1016/j.ccm.2015.08.009 -
The Medical Clinics of North America May 2021Comprehensive patient care requires an integrated approach that often includes different specialties. Of these specialties, Ophthalmology stands out with its variable... (Review)
Review
Comprehensive patient care requires an integrated approach that often includes different specialties. Of these specialties, Ophthalmology stands out with its variable pathologic conditions, unique tools, and special examination techniques, which are not part of the standard training of internal medicine or other specialties. The authors review prior studies focused on inpatient ophthalmology consultations, common reasons for inpatient ophthalmology consultation, and the recommended approach to the most common ocular complaints that could present to the inpatient provider. They also shed light on the basic ocular history and eye examination that should be obtained before requesting an ophthalmic evaluation.
Topics: Eye Diseases; Hospitalization; Humans; Ophthalmology; Patient Care; Referral and Consultation
PubMed: 33926647
DOI: 10.1016/j.mcna.2021.02.006