Novel compound heterozygous mutations in CNGA1in a Chinese family affected with autosomal recessive retinitis pigmentosa by targeted sequencing

Gene symbol list that include in the Hereditary Ophthalmological Disease GenePanel. (XLSX 12 kb

Cell-Free DNA Sequencing of Intraocular Fluid as Liquid Biopsy in the Diagnosis of Vitreoretinal Lymphoma

PurposeTo seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value.MethodsThe study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500μl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500μl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes.ResultsCfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P<0.001, adjusted R2 = 0.789, sensitivity 0.913, specificity 0.950); by comparison, the sensitivity and specificity of the vitreous cytopathology were 0.826 and 1.000, respectively. Further analysis of the mutation profile showed that patients carrying CD79B mutation tended to have higher intraocular interleukin-10 level (P=0.030), that CARD11 mutation was correlated with younger age at ocular onset (P=0.039), and that patients with intracranial involvement carried more multiple-site mutations in the BTG2 gene (P=0.013).ConclusionsThe improved workflow of CfDNA sequencing is of sound feasibility in a limited amount of vitreous humor. The logistic model based on the mutations could help to provide reliable clues for the diagnosis of VRL

Role of Fractalkine/CX3CR1 Interaction in Light-Induced Photoreceptor Degeneration through Regulating Retinal Microglial Activation and Migration

Background: Excessive exposure to light enhances the progression and severity of some human retinal degenerative diseases. While retinal microglia are likely to be important in neuron damage associated with these diseases, the relationship between photoreceptor damage and microglial activation remains poorly understood. Some recent studies have indicated that the chemokine fractalkine is involved in the pathogenesis of many neurodegenerative diseases. The present study was performed to investigate the cross-talk between injured photoreceptors and activated retinal microglia, focusing on the role of fractalkine and its receptor CX3CR1 in light-induced photoreceptor degeneration. Methodology/Principal Findings: Both in vivo and in vitro experiments were involved in the research. In vivo, Sprague– Dawley rats were exposed to blue light for 24 hours. In vitro, the co-culture of primary retinal microglia and a photoreceptor cell line (661W cell) was exposed to blue light for five hours. Some cultures were pretreated by the addition of anti-CX3CR1 neutralizing antibody or recombinant fractalkine. Expression of fractalkine/CX3CR1 and inflammatory cytokines was detected by immunofluorescence, real-time PCR, Western immunoblot analysis, and ELISA assay. TUNEL method was used to detect cell apoptosis. In addition, chemotaxis assay was performed to evaluate the impact of soluble fractalkine on microglial migration. Our results showed that the expression of fractalkine that was significantly upregulated after exposure to light, located mainly at the photoreceptors. The extent of photoreceptor degeneration and microglial migratio

A Synthesized Glucocorticoid- Induced Leucine Zipper Peptide Inhibits Retinal Müller Cell Gliosis

Purpose: The anti-inflammatory activities of protein glucocorticoid-induced leucine zipper (GILZ) have been demonstrated in vivo and in vitro. Here, we examined the potential effect of a synthetic peptide derived from the leucine zipper motif and proline-rich region of GILZ on suppressing inflammatory responses in primary cultured rat Müller cells.Methods: Peptides were selected from amino acids 98–134 of the GILZ protein (GILZ-p). Solid-phase peptide synthesis was used to generate the cell-penetrating peptide TAT, which was bound to the amino terminus of GILZ-p. Primary cultured retinal Müller cells were stimulated with lipopolysaccharide (LPS) alone or in combination with different concentrations of GILZ-p, and the interaction of GILZ-p with nuclear factor (NF)-κB p65 in Müller cells was investigated by western blotting, immunoprecipitation, and immunofluorescence. The expression of the Müller cell gliosis marker glial fibrillary acidic protein (GFAP), functional protein aquaporin (AQP)-4, and the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF) α, intercellular adhesion molecule (ICAM)-1, and monocyte chemoattractant protein (MCP)-1 was measured by Western Blotting. The concentration of those cytokines in culture medium was measured by using Enzyme-Linked Immunosorbent Assay.Results: The synthesized GILZ-p, which was water-soluble, entered cells and bound with NF-κB p65, inhibiting p65 nuclear translocation. GILZ-p inhibited the LPS-induced expression of GFAP, IL-1β, TNFα, ICAM-1, and MCP-1 in Müller cells and prevented the LPS-induced downregulation of AQP4.Conclusions: These results indicate that GILZ-p interacted with NF-κB p65 and suppressed p65 nuclear translocation, thereby inhibiting inflammatory cytokine release and Müller cell gliosis

COVID-19 Vaccine-Related Vogt–Koyanagi–Harada Disease Complicated by Central Serous Chorioretinopathy during Treatment Course: Case Report and Literature Review

With the promotion of mass COVID-19 vaccination in the elimination of the SARS-CoV-2 pandemic, new side effects, including ocular complications, are emerging. In this study, we report on a 62-year-old Chinese man who developed Vogt–Koyanagi–Harada (VKH) disease six days after his third dose of an inactivated COVID-19 vaccine, with a preceding severe headache and tinnitus. His medical history included tuberculosis 20 years prior and hypertension. Systemic prednisone was administered, resulting in completely relieved inflammation and improved visual acuity. Another three and a half months later, the visual acuity of his right eye slightly decreased due to complicated central serous chorioretinopathy (CSC) disease. By gradually replacing prednisone with cyclosporine within 2 months, the subretinal fluid was completely absorbed at the last visit. Steroid-related CSC during the treatment course of VKH disease after COVID-19 vaccination has never been reported before. By reviewing relative literature, we discuss the mechanism of CSC onset in our case and the potential therapeutic strategies. Complicated CSC may develop in the eyes with vaccine-related VKH after steroid treatment. Ophthalmologists should be aware of this condition, carefully distinguish complicated CSC with inflammation relapse, and adjust the medication in a timely manner

Clinical Features and Treatments of Syphilitic Uveitis: A Systematic Review and Meta-Analysis

Purpose. To investigate the clinical features and efficacies of treatments for syphilitic uveitis. Methods. PubMed was searched for studies of syphilitic uveitis published between January 1990 and October 2016. The clinical features were summarized and appraised. The pooled success rate was defined as an improved or maintained final visual acuity and was calculated with 95% confidence intervals (CIs). Heterogeneity, subgroup analysis, sensitivity analysis, and publication bias were assessed. Results. Thirty-two studies involving 670 patients were analyzed. The most common type of syphilitic uveitis was papillitis. The pooled success rate was 0.91 (95% CI 0.84–0.97) for antibacterial agents alone (15 studies, 286 patients); 0.95 (95% CI 0.91–0.98) for antibacterial agents and systemic corticosteroids combined (11 studies, 245 patients); and 0.91 (95% CI 0.80–0.98) for antibacterial agents, systemic corticosteroids, and other immunosuppressants combined (3 studies, 73 patients). Subgroup analyses revealed no correlations of the efficacy of antibacterial agent monotherapy with study characteristics, such as human immunodeficiency virus coinfection status. Conclusions. This systematic review and meta-analysis revealed the efficacy of antibacterial agents for treating syphilitic uveitis. Coadministration of systemic corticosteroids or immunosuppressants did not elicit further improvements in the clinical outcomes of antibacterial agents

Clinical Features and Surgical Outcomes of Posterior Segment Intraocular Foreign Bodies in Children in East China

Purpose. To report the long-term follow-up results of posterior segment intraocular foreign body (IOFB) removal in children and to determine the prognostic factors for visual outcome. Methods. Design: retrospective, noncomparative, interventional case series; a single tertiary care center study. Participants or samples: eleven eyes (11 patients) under 16 years of age with posterior segment IOFB injuries from May 2014 to November 2017. Main outcome measures: clinical features of injury, visual acuity, and complications. Results. The mean age was 6.8 years, and the mean follow-up was 20.2 months. The main IOFB sources were accidental penetration of the eye by materials in the playground (6 cases) or by pencil lead at school (4 cases). The mean IOFB size was 3.8 (range 1–6) mm. At the last visit, the visual acuities were 20/40 or better in 40.0% of patients and better than 20/200 in 70.0%. Poor visual outcome was correlated with intraoperative rhegmatogenous retinal detachment (P=0.0083). Postoperative complications included elevated transient intraocular pressure, retinal redetachment, and secondary glaucoma. Conclusions. The clinical features of pediatric posterior segment IOFBs suggest insufficient awareness of such injuries both on the playground and at school. Visual outcomes from surgical treatment were relatively favorable in this series

Rapid Progression of Foveomacular Retinoschisis in Young Myopics

PURPOSE: To describe a foveomacular retinoschisis that has not been described. METHODS: Patients with foveomacular retinoschisis were included. Exclusion criteria included refractive error over -6.00 diopters, presence of posterior staphyloma, positive RS1-gene mutation, family history of retinoschisis, optic disk abnormalities, or glaucoma. Vitrectomy was performed on eyes with functional or structural deterioration. RESULTS: Seventeen eyes from 10 patients (15-30 years old, 8 females and 2 males) with foveoschisis were recruited, with bilateral involvement in 7 patients and unilateral in 3 patients. Vitrectomy was performed in 13 eyes (13/17, 76.5%). Seven eyes (6 patients) were operated soon after the first presentation because of poor vision and severe foveoschisis. Six eyes (6 patients) were operated 2 weeks to 13 months later because of deterioration of vision and foveoschisis. Preoperative vision was 20/134 ± 20/165, and postoperative vision was 20/25 ± 20/57, with visual improvement of 6.9 (4-14) lines. The mean postoperative follow-up period was 36.5 (15-69) months. Four eyes (4 patients) were asymptomatic, despite progression of foveoschisis. Three eyes (3 patients) maintained normal macula structures. CONCLUSION: We report a foveomacular retinoschisis characterized by young age of onset, female predominant, no highly myopia, mostly bilateral involvement, and rapid progression of foveoschisis and visual acuity. Vitrectomy is effective in restoring anatomical structure and stabilize vision