ObjectiveTo reveal the pathogenic mutation in a three-generation Chinese family with autosomal dominant familial exudative vitreoretinopathy (FEVR). MethodsThree patients and a healthy spouse from the index family with FEVR were recruited. The proband was a 5 years old boy. His mother and grandpa were presented with typical FEVR presentations, while his father with normal ocular fundus. DNA was extracted from peripheral blood samples taken from all four participants. All coding and exon-intron boundary regions of five targeted genes, including NDP, FZD4, LRP5, TSPAN12 and ZNF408 were amplified with polymerase chain reaction and sequenced using direct sequencing. In silico analyses were applied to determine the conservation of the mutation site, pathogenic effect and the potential protein crystal structural changes caused by the mutation. ResultsFZD4 c.478G > A, a susceptible mutation was found after four high frequency mutation sites which MAF values were higher than 0.001 was filtered among 5 single nucleotide variations detected in four participants, leading to the residue 160 changing from glutamate to lysine (p.E160K). Co-segregation analysis between genotypes and phenotypes revealed FZD4 p.E160K as the disease-causing mutation for this family. Conservational analysis suggested that this mutation site was highly conserved among all tested species. Functional analysis predicated that this mutation may be a damaging mutation. Crystal structural analysis also indicated that this mutation could lead to the elimination of the hydrogen bond between residue 160 and asparagine at residue 152, thus altering the tertiary structure of the protein and further impairing the protein function. ConclusionOur study demonstrates FZD4 p.E160K as a novel pathogenic mutation for FEVR.
The clinical manifestations of infectious retinal diseases are complicated, especially these result from serious infectious diseases such as acquired immune deficiency syndrome (AIDS), tuberculosis and syphilis infections. It is an important issue to differentiate infectious retinal disease from noninfectious intraocular inflammation in the clinic. It is, therefore, highly desirable to follow a proper steps to reach the correct diagnosis. Complete history review and comprehensive ocular examination remains the first step in diagnosing infectious retinal diseases. Although an array of laboratory and serological tests are available to assist in the diagnosis, some situations may require a diagnostic therapy or a tissue biopsy. Identification of the pathogen and histopathologic examination of the ocular specimen remain to be the gold standard of diagnosis. Initiation a specific and appropriate antimicrobial therapy needs multidisciplinary collaborations including ophthalmologists and infectious specialists. Updated knowledge of general medicine and management of infectious diseases, interdisciplinary collaborations and optimization of treatment processes will improve the diagnosis and treatment of retinal infectious diseases in the future.
ObjectiveTo investigate the clinical characteristics of 40 patients with ocular toxocariasis (OT) on the first attendance. MethodsA total of 40 consecutive patients who were clinically and serologically diagnosed with OT were retrospectively reviewed. ResultsThe mean age of patients was (12.12±10.42) years. There were 29 males and 11 females. 29 cases presented with decreased vision, 4 children with leukocoria, 2 cases with strabismus and 5 cases was found abnormal during regular eye examination. Initially 8 eyes (20%) were misdiagnosed as retinoblastoma (1 eye), Coat's disease(1 eye), cataract (2 eyes), iridocyclitis (2 eyes) and retinal detachment (2 eyes). 23 eyes had retinal detachment, 19 eyes had cataract. OT was the initial diagnosis for 15 patients (37.5%). The best corrected visual acuity (BCVA) were NLP to 0.7. Ultrasound biomicroscopy (UBM) were performed in 29 eyes, and identified peripheral granulomas in 23 eyes and adjacent tractional retinal detachment in 12 eyes. We also identified 17 cases (68.0%) with elevated IgE level among 25 patients with positive serological antibody test. ConclusionsTractional retinal detachment, vitreous opacities and cataract are the common clinical findings at the first attendance of OT patients. The adjunctive test of serum total IgE level may be helpful for the diagnosis. The application of UBM and specific IgG detection in serum and intraocular fluid, can also improve the diagnosis.
Objective To investigate the relationship of clinical indexes between retinopathy in systemic-lupus-erythematosus （SLE）nephritis and SLE，and to discuss its clinical significance. Method The clinical data of 43 cases of SLE nephritis with ocular fundus diseases were retrospectively analyzed.The relationships between retinopathy and kidney defect，general lesions，SLEDAI grade，antinuclear antibody （ANA），anti-double stranded DNA，complement 3 and antiphospholipid antibodies were analyzed with Logistic regression respectively. Results In 86 eyes of the43paitents，there were retinal cotton wool spots in51eyes（59.3%），edema of optic disk in 43 eyes（50.5%），retinal haemorrhage in 12 eyes（14.0%），retinal artery occlusion in 5 eyes（5.8%），central retinal vein occlusion in 2 eyes（2.3%），retinal detachment in 3 eyes（3.5%），optic atrophy in 2 eyes（2.3%），and neovascularization in 2 eyes（2.3%）.Logistic regression analysis revealed that SLEDAI grade had linear dependent relation with cotton wool spots and optic disk edema（chi;2=42.154，6.498;P＜0.001），and didnrsquo;t have any correlation with proteinuria，hematuria and kidney function.Linear relation between retinal vascular occlusion and antiphospholipid antibodies was found（chi;2=24.475，P＜0.001）.Retinal haemorrhages，retinal detachment，optic atrophy and neovascularization did not correlate with clinical features. Conclusion SLEDAI grade had linear dependent relation with cotton wool spots and optic disk edema in patients with SLE nephritis，and Linear relation between retinal vascular occlusion and antiphospholipid antibodies is ascertained. Ocular fundus diseases are clinically important for evaluating the therapeutic responses and prognosis in lupus nephritis. (Chin J Ocul Fundus Dis, 2006, 22: 239-241)
Retinal macrophages and (or) microglial cells play important roles in regulating inflammation, angiogenesis and tissue repairing, thus affect the development and prognosis of ischemic retinal disease, ocular immune diseases and ocular tumors. Reversing the polarization imbalance of these cells may provide new therapeutic strategies for ischemic retinal disease and ocular immune diseases. The duality of the polarization direction of these cells is still controversial in the inflammatory reaction and pathological angiogenesis of ischemic retinal disease. Meanwhile, the plasticity and diversity of the function need to be further studied and discussed.
Hypertensive retinopathy (HR) often coexist with carotid lesions in hypertensive patients. Carotid lesions are closely associated with cardiovascular and cerebrovascular diseases, as well as end events, offering early important evidence to screening high risk patients. HR has significant value to predict target organ damage (TOD) of hypertension including carotid lesion. In addition, hypertensive retinopathy and carotid lesions-related ischemic ocular diseases will cause serious vision function damage. This article is going to summarize the value and correlation between hypertensive retinopathy and carotid lesions in terms of clinical manifestations, pathological physiological mechanism and target organ damage.
Purpose To investigate the expression of the interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-alpha;) in epiretinal membranes(ERM) of eyes with proliferative vitreoretinopathy(PVR). Methods Nineteen epiretinal membranes were obtained form eyes undergoing vitrectomy for retinal detachment complicated with PVR and observed by immunohistochemical methods. Results Expression of IL-6 and TNF-alpha; were observed in 12 and 15 membranes respectively with positive staining mostly in extracellular matrix of epiretinal membranes.Only one membrane showed positive to IL-6 intracellularly,and expression for IL-6 and TNF-alpha; simultaneously in membranes. Conclusion The findings indicate that IL-6、and TNF-alpha;might be involved in the development of PVR. (Chin J Ocul Fundus Dis,1998,14:219-221)
Retinal angiomatous proliferation (RAP) is a genetic distinct subgroup of exudative age-related macular degeneration which shows a rapid and severe vision loss and high recurrence rates. The pathophysiological mechanisms of RAP is unclear. Recent histopathologic study and en face optical coherence tomography angiography have furthered our understanding of RAP. Clinical features frequently associated with RAP include bilateral disease, presence of reticular pseudodrusen and pigment epithelial detachments. Indocyanine green angiography is the gold standard diagnostic tool. Recently, more and more accurate optical coherence tomography has improved the acknowledgement of stage and diagnosis of RAP. The treatment efficacy of RAP is highly dependent on the stage. Anti-vascular endothelial growth factor therapy is currently the first line of treatment. Other treatment options including combination of photodynamic therapy with antiangiogenic agent intravitreal injections also achieve a reasonable therapeutic outcome. There remain several important questions such as pathogenesis and treatment regimen, to be answered in future RAP research studies.
ObjectiveTo identify mutations in NDP, FZD4, LRP5, TSPAN12 in Chinese families with familial exudative vitreoretinopathy (FEVR) and observe the clinical features.MethodsRetrospective case series study. The 9 patients (18 eyes) and 5 normal members from 4 unrelated families were included in the study. The patients medical history and family history were collected in detail. All patients underwent best corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus colorized photography, fundus fluorescein angiography (FFA). Genomic DNA were collected from all the patients. Mutations were detected by directly sequencing to the whole coding region and exon-intron boundaries of NDP, FZD4, LRP5 and TSPAN12 gene. Polyphen and SIFT programs were used to predict the effects on the structure and functional properties of mutant protein.ResultsThere were two affected individuals in the family 2 carried LRP5 gene mutation [c.1330C＞T (p.R444C )] in exon 6 by sequence analysis. A score of 0.882 was acquired by Polyphen program analysis. And the missense change was predicted to be pathogenic by SIFT. Fundus changes of the proband showed angioplasia, tortuosity of peripheral vessels. And temporal dragging of the optic disc, peripheral avascular zone, neovascularization were found in FFA. Brush-like and straight of peripheral vessels were found in Ⅰ1. No variant was found in NDP, FZD4 and TSPAN12 gene.ConclusionOur study supports the gene mutation c.1330C＞T (p.R444C) of LRP5 is pathogenesis of FEVR. Patients with the same mutation could have variable phenotypic characteristics.
Purpose To investigate the expression of intercellular adhesion molecules ICAM-1 and Mac-1，in epiretinal membanes (ERM) of eyes wi th proliferative vitreoretinopathy (PVR)． Methods Twenty epiretinal membranes were obtained from eyes undergone vitrectomy for retinal detachment complicated with PVR and observed by immunohistochemical examination． Results Expressions of ICMA-1 and Mac-1 were observed in 18 and 15 membranes respectively．Expression of both adhesion molecules in 12 membranes． Conclusion The findings indicate that adhesion molecules might be involved in the development of PVR． (Chin J Ocul Fundus Dis，2000，16：71-138)