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American Journal of Ophthalmology Jan 2021To elucidate molecular risk factors for posterior segment uveitis using a functional genomics approach.
OBJECTIVE
To elucidate molecular risk factors for posterior segment uveitis using a functional genomics approach.
DESIGN
Genetic association cohort study.
METHODS
Setting: Single-center study at an academic referral center.
STUDY POPULATION
164 patients with clinically diagnosed uveitis of the posterior segment.
MAIN OUTCOME MEASURES
Exome sequencing was used to detect variants identified in 164 patients with posterior segment uveitis. A phenotype-driven analysis, protein structural modeling, and in silico calculations were then used to rank and predict the functional consequences of key variants.
RESULTS
A total of 203 single nucleotide variants, in 23 genes across 164 patients, were included in this study. Both known and novel variants were identified in genes previously implicated in specific types of syndromic uveitis-such as NOD2 (Blau syndrome) and CAPN5 NIV (neovascular inflammatory vitreoretinopathy)-as well as variants in genes not previously linked to posterior segment uveitis. Based on a ranked list and protein-protein-interaction network, missense variants in NOD-like receptor family genes (NOD2, NLRC4, NLRP3, and NLRP1), CAPN5, and TYK2 were characterized via structural modeling and in silico calculations to predict how specific variants might alter protein structure and function. The majority of analyzed variants were notably different from wild type.
CONCLUSIONS
This study implicates new pathways and immune signaling proteins that may be associated with posterior segment uveitis susceptibility. A larger cohort and functional studies will help validate the pathogenicity of the mutations identified. In specific cases, whole-exome sequencing can help diagnose nonsyndromic uveitis in patients harboring known variants for syndromic inflammatory diseases.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Calpain; Child; Child, Preschool; Female; Genetic Association Studies; Humans; Inflammasomes; Male; Middle Aged; Mutation, Missense; NLR Proteins; Proteomics; TYK2 Kinase; Uveitis, Posterior; Exome Sequencing
PubMed: 32707200
DOI: 10.1016/j.ajo.2020.07.021 -
Indian Journal of Ophthalmology Apr 2013Literature review for indocyanine green angiography and evaluate the role of indocyanine green angiogram (ICGA) in patients with posterior uveitis seen at a tertiary... (Review)
Review
Literature review for indocyanine green angiography and evaluate the role of indocyanine green angiogram (ICGA) in patients with posterior uveitis seen at a tertiary referral eye care centre. Detailed review of the literature on ICGA was performed. Retrospective review of medical records of patients with posterior uveitis and dual fundus and ICGA was done after institutional board approval. Eighteen patients (26 eyes) had serpiginous choroiditis out of which 12 patients had active choroiditis and six patients had healed choroiditis, six patients (12 eyes) had ampiginous choroiditis, six patients (12 eyes) had acute multifocal posterior placoid pigment epitheliopathy, eight patients (10 eyes) had multifocal choroiditis, four patients (eight eyes) had presumed ocular histoplasmosis syndrome, four patients (eight eyes) had presumed tuberculous choroiditis, two patients (four eyes) had multiple evanescent white dot syndrome and two patients (four eyes) had Vogt Koyanagi Harada (VKH) syndrome. The most characteristic feature noted on ICGA was the presence of different patterns of hypofluorescent dark spots, which were present at different stages of the angiogram. ICGA provides the clinician with a powerful adjunctive tool in choroidal inflammatory disorders. It is not meant to replace already proven modalities such as the fluorescein angiography, but it can provide additional information that is useful in establishing a more definitive diagnosis in inflammatory chorioretinal diseases associated with multiple spots. It still needs to be determined if ICGA can prove to be a follow up parameter to evaluate disease progression.
Topics: Choroiditis; Fluorescein Angiography; Humans; Indocyanine Green; Uveitis, Posterior
PubMed: 23685486
DOI: 10.4103/0301-4738.112159 -
Eye (London, England) Jan 2021The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that... (Review)
Review
The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionized imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardized and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The first part of this imaging review will deal with noninvasive imaging methods, focusing on fundus autofluorescence and optical coherence tomography as well as recent developments in imaging of the posterior segment.
Topics: Fluorescein Angiography; Humans; Optical Imaging; Retinal Vessels; Tomography, Optical Coherence; Uveitis; Uveitis, Posterior
PubMed: 32678354
DOI: 10.1038/s41433-020-1063-1 -
Trials Dec 2017Uveitis, a group of disorders characterised by intraocular inflammation, causes 10-15% of total blindness in the developed world. The most sight-threatening uveitis...
BACKGROUND
Uveitis, a group of disorders characterised by intraocular inflammation, causes 10-15% of total blindness in the developed world. The most sight-threatening uveitis affects the posterior segment of the eye (posterior-segment involving uveitis (PSIU)). Numerous different outcomes have been used in clinical trials evaluating alternative treatments for uveitis, limiting inter-trial comparison and aggregation of data. We aim to develop a core outcome set (COS) that would provide a standardised set of outcomes to be measured and reported in all effectiveness trials for PSIU.
METHODS
A three-phase design will be used informed by recommendations from the Core Outcome Measures in Effectiveness Trials (COMET) initiative. Phase 1: a comprehensive list of outcomes will be identified through both a systematic review of effectiveness trials of PSIU and qualitative research with stakeholders. The qualitative study will comprise focus groups with patients and their carers in parallel with one-to-one telephone interviews with health professionals and policy-makers. In the focus groups, patients will be grouped according to whether or not their uveitis is complicated by the sight-threatening condition uveitic macular oedema (UMO) since it is hypothesised that the presence of UMO may significantly impact on patient experience of PSIU. Phase 2: Delphi methodology will be used to reduce the range of potential outcomes for the core set. Up to three Delphi rounds will be used through an online survey. Participants will be asked to rate the importance of each outcome on a 9-point Likert scale where 9 is most important. Phase 3: a consensus meeting will be held with key stakeholders to discuss the Delphi results and ratify the final outcomes to be included in the COS.
DISCUSSION
The development of an agreed COS for PSIU would help ensure that outcomes which matter to key stakeholders are captured and reported in a consistent way. A COS for PSIU would allow greater comparison and aggregation of data across trials for the better evaluation of established and emerging therapies through evidence synthesis and meta-analysis to inform clinical guidelines and health policy.
TRIAL REGISTRATION
COMET. http://comet-initiative.org/studies/details/640 . August 2015.
Topics: Clinical Trials as Topic; Consensus; Delphi Technique; Endpoint Determination; Focus Groups; Humans; Interdisciplinary Communication; Interviews as Topic; Research Design; Stakeholder Participation; Systematic Reviews as Topic; Treatment Outcome; Uveitis, Posterior
PubMed: 29191216
DOI: 10.1186/s13063-017-2294-8 -
Survey of Ophthalmology 2023An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for... (Review)
Review
An array of retinochoroid imaging modalities aid in comprehensive evaluation of the immunopathological changes in the retina and choroid, forming the core component for the diagnosis and management of inflammatory disorders such as uveitis. The recent technological breakthroughs have led to the development of imaging platforms that can evaluate the layers of retina and choroid and the structural and functional alteration in these tissues. Ophthalmologists heavily rely on imaging modalities such as dye-based angiographies (fluorescein angiography and indocyanine green angiography), optical coherence tomography, fundus autofluorescence, as well as dye-less angiography such as optical coherence tomography angiograph,y for establishing a precise diagnosis and understanding the pathophysiology of the diseases. Furthermore, these tools are now being deployed with a 'multimodal' approach for swift and accurate diagnosis. In this comprehensive review, we outline the imaging platforms used for evaluation of posterior uveitis and discuss the organized, algorithmic approach for the assessment of the disorders. Additionally, we provide an insight into disease-specific characteristic pathological changes and the established strategies to rule out disorders with overlapping features on imaging.
Topics: Humans; Multimodal Imaging; Uveitis, Posterior; Uveitis; Fluorescein Angiography; Fundus Oculi; Tomography, Optical Coherence; Choroid
PubMed: 36724831
DOI: 10.1016/j.survophthal.2023.01.006 -
Ophthalmic Research 2013Emergent and resurgent arthropod vector-borne diseases are major causes of systemic morbidity and death and expanding worldwide. Among them, viral and bacterial agents... (Review)
Review
Emergent and resurgent arthropod vector-borne diseases are major causes of systemic morbidity and death and expanding worldwide. Among them, viral and bacterial agents including West Nile virus, Dengue fever, Chikungunya, Rift Valley fever, and rickettsioses have been recently associated with an array of ocular manifestations. These include anterior uveitis, retinitis, chorioretinitis, retinal vasculitis and optic nerve involvement. Proper clinical diagnosis of any of these infectious diseases is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by the detection of a specific antibody in serum. Ocular involvement associated with emergent infections usually has a self-limited course, but it can result in persistent visual impairment. There is currently no proven specific treatment for arboviral diseases, and therapy is mostly supportive. Vaccination for humans against these viruses is still in the research phase. Doxycycline is the treatment of choice for rickettsial diseases. Prevention, including public measures to reduce the number of mosquitoes and personal protection, remains the mainstay for arthropod vector disease control. Influenza A (H1N1) virus was responsible for a pandemic human influenza in 2009, and was recently associated with various posterior segment changes.
Topics: Animals; Communicable Diseases, Emerging; Disease Vectors; Eye Infections; Humans; Uveitis, Posterior
PubMed: 23258387
DOI: 10.1159/000344009 -
Eye (London, England) Jan 2021The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that... (Review)
Review
The aim of this review was to identify the imaging methods at our disposal to optimally manage posterior uveitis at the present time. The focus was put on methods that have become available since the 1990s, some 30 years after fluorescein angiography had revolutionised imaging of posterior uveitis in particular imaging of the retinal vascular structures in the 1960s. We have focussed our review on precise imaging methods that have been standardised and validated and can be used universally thanks to commercially produced and available instruments for the diagnosis and follow-up of posterior uveitis. The second part of this imaging review will deal with invasive imaging methods and in particular ocular angiography.
Topics: Diagnostic Tests, Routine; Fluorescein Angiography; Humans; Retinal Vessels; Uveitis; Uveitis, Posterior
PubMed: 32778739
DOI: 10.1038/s41433-020-1072-0 -
International Ophthalmology Clinics 1995
Review
Topics: Autoimmune Diseases; Bacterial Infections; Clinical Laboratory Techniques; Fluorescein Angiography; Humans; Mycoses; Parasitic Diseases; Uveitis, Posterior; Virus Diseases
PubMed: 8964666
DOI: 10.1097/00004397-199503530-00006 -
Survey of Ophthalmology 2017
Topics: Humans; Uveitis; Uveitis, Posterior
PubMed: 28606632
DOI: 10.1016/j.survophthal.2017.06.004 -
Klinische Monatsblatter Fur... Dec 2023Intermediate and posterior uveitis describes a broad variety of different types of intraocular inflammation. Before starting treatment of intermediate or posterior...
Intermediate and posterior uveitis describes a broad variety of different types of intraocular inflammation. Before starting treatment of intermediate or posterior uveitis, a differentiation between infectious or non-infectious uveitis must always be made. Pathognomonic symptoms do not exist, visual loss and vitreous floaters are the most common symptoms. The indication for therapy is influenced by the anatomical localization, the degree of inflammation, an association, complications and the activity of the inflammation. In addition to clinical ophthalmological standard examination, angiography and OCT are the most important investigations to classify and assess the course of inflammation. Macular edema is the most common complication of intermediate or posterior uveitis and should be treated at first onset, recurrence, or worsening. Oral, intravenous, or intravitreal corticosteroids are usually the primary therapy for intermediate or posterior uveitis. Systemic immunosuppression is indicated after steroid failure in non-infectious uveitis.
Topics: Humans; Uveitis, Posterior; Uveitis; Inflammation; Algorithms; Uveitis, Intermediate; Glucocorticoids
PubMed: 37977203
DOI: 10.1055/a-2193-2509