14 research outputs found

    Tantalum Surgical Clip Presenting As an Intraorbital Foreign Body

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    This is a Photo Essay and does not have an abstract. Please download the PDF or view the article in HTML

    Missense mutation outside the forkhead domain of FOXL2 causes a severe form of BPES type II

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    Purpose: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a developmental disease characterized by a complex eyelid malformation associated or not with premature ovarian failure (POF). BPES is essentially an autosomal dominant disease, due to mutations in the forkhead box L2 (FOXL2) gene, encoding a forkhead transcription factor. More than one hundred unique FOXL2 mutations have been described in BPES in different populations, many of which are missense mutations in the forkhead domain. Here, we report on a very severe form of BPES resulting from a missense mutation outside the forkhead domain. Methods: A clinical and molecular genetic investigation was performed in affected and unaffected members of an Iranian family with BPES. The FOXL2 coding region was sequenced in an index case. Targeted mutation testing was performed in 8 family members. Results: We have identified a heterozygous FOXL2 missense mutation c.650C -> G (p.Ser217Cys) co-segregating with disease in members of a three-generation family with BPES type II. Only few missense mutations have been reported outside the forkhead domain so far. They were all found in mild BPES, in line with in vitro studies demonstrating mostly normal localization and normal or increased transactivation properties of the mutant proteins. Unlike previous studies, affected members of the family studied here showed a severe BPES phenotype, with bilateral amblyopia due to uncorrected ptosis. Conclusions: This is the first study demonstrating a severe BPES phenotype resulting from a FOXL2 missense mutation outside the forkhead domain, expanding our knowledge about the phenotypic consequences of missense mutations outside the forkhead domain in BPES

    Diffuse Pigment Release in a Patient Undergoing Tumor-Infiltrating Lymphocyte Immunotherapy for Acral Malignant Melanoma

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    This is a Photo Essay and does not have an abstract. Please download the PDF or view the article in HTML

    Photodynamic therapy and intravitreal bevacizumab with versus without triamcinolone for neovascular age-related macular degeneration; a randomized clinical trial

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    Purpose: To compare the outcomes of photodynamic therapy (PDT) combined with intravitreal bevacizumab (IVB) with versus without intravitreal triamcinolone (IVT) in neovascular age-related macular degeneration (AMD). Methods: Eighty-four eyes with active CNV secondary to AMD with no prior treatment were enrolled and followed for 1-year. Eligible eyes were randomly assigned to either PDT/IVB or PDT/IVB/IVT. The main outcome measure was change in best-corrected visual acuity (BCVA). Results: Mean patient age was 71 ΁ 9 years. BCVA changes from baseline were statistically significant in both study arms at all follow-up intervals, however no significant difference was observed between the two groups regarding BCVA changes at week 12 (95% CI:-0.11-0.12 LogMAR) and other time points (all P > 0.6). Mixed model analysis revealed a significant effect from age (P < 0.001), pigment epithelial detachment (P = 0.009) and baseline BCVA (P < 0.001) on visual improvement. Significant central macular thickness (CMT) reduction occurred at all-time points as compared to baseline in both groups which was comparable between the study arms. There was no significant difference between the study arms in terms of retreatment rate (P = 0.1) and survival to the first repeat IVB injection (P = 0.065). Conclusion: Additional low-dose IVT to a PDT/IVB regimen for neovascular AMD provided no beneficial effects in terms BCVA or CMT, yet demonstrated a trend toward extending the injection-free period

    Short chain fatty acids inhibit endotoxin-induced uveitis and inflammatory responses of retinal astrocytes.

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    Short chain fatty acids (SCFAs) are produced by gut microbiota as fermentation products of digestion-resistant oligosaccharides and fibers. Their primary roles are functioning as major energy sources for colon cells and assisting in gut homeostasis by immunomodulation. Recent evidence suggests that they affect various organs both at cellular and molecular levels, and regulate functions in distance sites including gene expression, cell proliferation, cell differentiation, apoptosis and inflammation. In this study, we examined whether SCFAs are present in the mouse eye and whether SCFAs affect inflammatory responses of the eye and retinal astrocytes (RACs). We observed that intra-peritoneal injected SCFAs were detected in the eye and reduced intraocular inflammation induced by lipopolysaccharide (LPS). Moreover, SCFAs displayed two disparate effects on LPS-stimulated RACs - namely, cytokine and chemokine production was reduced, but the ability to activate T cells was enhanced. Our results support the existence of gut-eye cross talk and suggest that SCFAs can cross the blood-eye-barrier via the systemic circulation. If applied at high concentrations, SCFAs may reduce inflammation and impact cellular functions in the intraocular milieu

    Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous <i>COL18A1</i> Mutation Causing Knobloch Syndrome

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    <div><p>The aim of this study was to identify the genetic basis of a chorioretinal dystrophy with high myopia of unknown origin in a child of a consanguineous marriage. The proband and ten family members of Iranian ancestry participated in this study. Linkage analysis was carried out with DNA samples of the proband and her parents by using the Human SNP Array 6.0. Whole exome sequencing (WES) was performed with the patients’ DNA. Specific sequence alterations within the homozygous regions identified by whole exome sequencing were verified by Sanger sequencing. Upon genetic analysis, a novel homozygous frameshift mutation was found in exon 42 of the <i>COL18A1</i> gene in the patient. Both parents were heterozygous for this sequence variation. Mutations in <i>COL18A1</i> are known to cause Knobloch syndrome (KS). Retrospective analysis of clinical records of the patient revealed surgical removal of a meningocele present at birth. The clinical features shown by our patient were typical of KS with the exception of chorioretinal degeneration which is a rare manifestation. This is the first case of KS reported in a family of Iranian ancestry. We identified a novel disease-causing (deletion) mutation in the <i>COL18A1</i> gene leading to a frameshift and premature stop codon in the last exon. The mutation was not present in SNP databases and was also not found in 192 control individuals. Its localization within the endostatin domain implicates a functional relevance of endostatin in KS. A combined approach of linkage analysis and WES led to a rapid identification of the disease-causing mutation even though the clinical description was not completely clear at the beginning.</p></div

    Homozygosity Mapping and Whole Exome Sequencing Reveal a Novel Homozygous <i>COL18A1 - Figure 3 </i> Mutation Causing Knobloch Syndrome

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    <p>a. Sanger sequencing of <i>COL18A1</i> mutation NM_130445.2:c.3825_3838del:p.Ser1276Alafs*9 (Exon 42) comparing a wild type sequence (top), homozygous deletion in index patient IV-1 (middle) and heterozygous deletion in father of the index patient (bottom). b. Conservation of the deleted nucleotides across various species. c. Alignment of three isoforms of <i>COL18A1</i> and endostatin. The highlighted region is deleted in patient IV-1.</p
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