The aim of this paper was to report the cases of 3 consecutive patients with mitogen-activated protein kinase kinase inhibitor (MEKi)-associated retinopathy with characteristic multiple serous retinal detachments (SRDs). A functional analysis of the retinal pigment epithelium was performed in 2 patients by electro-oculography (EOG). In all 3 patients, SRD lesions were observed in the posterior pole including the fovea of both eyes.
View Article and Find Full Text PDFTo identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: P < 1.0 × 10).
View Article and Find Full Text PDFPurpose: To evaluate 1-year outcomes of intravitreal injections of aflibercept (IVA) in Japanese polypoidal choroidal vasculopathy (PCV) patients.
Methods: In this prospective, open-label, single-arm multicenter clinical trial, treatment-naïve PCV patients received IVA (2.0 mg) every 2 months, after 3 initial monthly doses.
Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analysed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method.
View Article and Find Full Text PDFThis study characterizes the kallikrein-kinin system in vitreous from individuals with diabetic macular edema (DME) and examines mechanisms contributing to retinal thickening and retinal vascular permeability (RVP). Plasma prekallikrein (PPK) and plasma kallikrein (PKal) were increased twofold and 11.0-fold (both P < 0.
View Article and Find Full Text PDFBackground: Neovascular glaucoma (NVG) is a serious complication for patients with proliferative diabetic retinopathy (PDR). Bevacizumab is a full-length humanized monoclonal antibody that binds all isoforms of vascular endothelial growth factor (VEGF). Recently, encouraging results regarding the off-label use of intravitreal bevacizumab (IVB) for the treatment of NVG have been reported.
View Article and Find Full Text PDFCase Report: To report the case of a 26-year-old woman with a family history of dominant optic atrophy who requested DNA testing and counselling. Ophthalmologic examination showed her affected father had bilateral temporal papillary pallor. Direct genomic sequencing of the OPA1 gene revealed a novel heterozygous nonsense mutation (Arg879stop).
View Article and Find Full Text PDFRetinal pigment epithelial cells (RPEs) are thought to be one of the main components of fibrous membrane observed in eyes with proliferative vitreo-retinopathy. We investigated the signalling mechanisms of TGF-beta2-dependent collagen gel contraction by RPEs. An in vitro type I collagen gel contraction assay was performed to evaluate the effect of TGF-beta2 on gel contraction.
View Article and Find Full Text PDFPurpose: To identify the genetic defect in the FZD4 gene responsible for familial exudative vitreoretinopathy (FEVR) in a Japanese family.
Design: Interventional case report.
Methods: Complete ophthalmologic examinations were performed, and the FZD4 gene was analyzed by direct genomic sequencing.
Purpose: To investigate the functional properties and intracellular signaling of hyalocytes under platelet-derived growth factor (PDGF)-rich conditions.
Methods: The hyalocytes were isolated from bovine eyes and identified by immunocytochemistry and electron microscope. The expression of PDGF receptor alpha/beta and its phosphorylation in response to PDGF-BB was analyzed by Western blot analysis.
Graefes Arch Clin Exp Ophthalmol
September 2004
Background: The purpose of this study is to investigate the effect of fibrinogen on angiogenesis in vitro formed by cultured bovine choroidal endothelial cells (BCECs) and the involvement of vascular endothelial growth factor (VEGF) in this mechanism.
Methods: For in vitro tube formation assay, BCECs were seeded on collagen gel containing fibrinogen (0-1.5 mg/ml).
Purpose: To describe a Japanese patient with lattice corneal dystrophy type I (LCD I) who lacked the typical lattice lines.
Design: Interventional case report.
Methods: A complete ophthalmologic examination was performed on a 54-year-old woman, and the TGFBI gene was analyzed by direct genomic sequencing.
Purpose: To study the advantages and complications of triamcinolone acetonide (TA)-assisted pars plana vitrectomy (PPV) for various retinal diseases.
Methods: This report is an interventional case series and nonrandomized study. One hundred seventy-seven eyes from 158 patients underwent PPV with or without TA.
Graefes Arch Clin Exp Ophthalmol
September 2003
Background: We investigated the role of the VEGF-VEGF receptor 2 (KDR) system in the development of choroidal neovascularization (CNV) and its possibility as a therapeutic target utilizing KDR selective receptor tyrosine kinase (RTK) inhibitor (SU5416) both in vitro and in an experimental CNV model.
Methods: VEGF-induced phosphorylation of KDR and p44/p42 MAPK in cultured bovine choroidal endothelial cells (BCECs) was determined by Western blot analysis. The proliferation and in vitro tube formation were analyzed by [3H]thymidine uptake and three-dimensional collagen gel model.
Adrenomedullin (AM) is a multifunctional peptide with various physiological actions, including vasodilatation, a defense mechanism against microorganisms, the regulation of growth and the regulation of insulin and glucose. In this study, we measured the vitreous AM levels in patients with diabetes mellitus to determine its potential involvement in the pathogenesis of diabetic retinopathy (DR). We used an immunoradiometric assay to measure the vitreous AM concentrations in a total of 28 eyes: 13 with DR and 15 with macular holes (15 men and 13 women, 62.
View Article and Find Full Text PDFGraefes Arch Clin Exp Ophthalmol
December 2002
Purpose: To investigate the causal relationship between VEGF and tissue factor (TF) expression, and its intracellular signaling in the retinal capillary endothelium both in vitro and in vivo.
Methods: TF mRNA and protein expression in cultured bovine retinal capillary endothelial cells (BRECs) were detected by RT-PCR and western blotting. The expression and subcellular localization of Egr-1 were analyzed by immunocytochemistry and western blotting.
Purpose: To investigate the factors that influence the visual-changing pattern in proliferative diabetic retinopathy even after successful vitrectomy.
Methods: One hundred and forty-seven consecutive eyes were retrospectively reviewed for 6-48 (average 20) months, and were divided into the following 4 groups based on their changing pattern of vision: group A, the visual acuity improved postoperatively and maintained the maximal corrected vision throughout the observation period (n = 49); group B, the visual acuity improved postoperatively but deteriorated thereafter (n = 68); group C, the visual acuity remained the same as before operation (n = 17), and group D, the visual acuity deteriorated immediately after vitrectomy (n = 13). Various issues including systemic conditions, blood tests, preoperative ocular findings, the operative procedures and postoperative complications were reviewed based on the patient records.