Search

Background and Objective: To study the relationship between baseline morphologic characteristics of the choroidal neovascular (CNV) lesion and long-term development of macular atrophy in eyes with neovascular age-related macular degeneration (AMD) treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA)., Patients and Methods: Certified graders evaluated baseline and 7-year follow-up (SEVEN-UP study) images of 41 eyes from the MARINA/ANCHOR and HORIZON trials. Using GRADOR software and stepwise linear regression, graders correlated lesion characteristics on fluorescein angiography (FA) at both visits with areas of definite decreased autofluorescence (DDAF) on fundus autofluorescence (FAF) imaging at the SEVEN-UP visit., Results: Three of 41 eyes (7.3%) had macular atrophy on FA at baseline (mean ± standard deviation [SD] size: 0.29 mm(2) ± 1.50 mm(2)), 29 (70.7%) at SEVEN-UP (mean ± standard deviation [SD] area: 7.42 mm(2) ± 7.97 mm(2)). On FAF imaging at the SEVEN-UP visit, all 41 eyes (100%) had DDAF (mean ± SD size: 10.29 mm(2) ± 8.07 mm(2)). Variables significantly associated with area of DDAF at the SEVEN-UP visit were the area of leaking CNV lesion components (coefficient: 0.953; P < .001), the area of other lesion components (coefficient: 1.094; P = .038), and the area of retinal pigment epithelial (RPE) atrophy (coefficient: 1.334; P = .040) on baseline FA imaging., Conclusion: The area of DDAF at more than 7 years after initiation of ranibizumab therapy was 35% larger than the original CNV lesion. The baseline area of leaking CNV and other components of the CNV lesion and the baseline area of RPE atrophy were important predictors of the area of definite decreased autofluorescence, presumably corresponding to areas of photoreceptor and RPE loss. The findings from this study may guide hypothesis generation for future AMD trials., (Copyright 2016, SLACK Incorporated.)

Aim: To evaluate the efficacy and safety of active removal of silicone oil with low and high viscosity through a 23-gauge transconjunctival cannula using an external vacuum pump., Methods: This study was conducted as a prospective, interventional case series. A total of 22 eyes of 21 patients [1000 centistokes (cSt): 17 eyes, 5700 cSt: 5 eyes] were included in this study. All patients underwent active silicone oil removal via the entire lumen of a 23-gauge microcannula with suction pressure of a 650-700 mm Hg vacuum using an external vacuum pump. A tubing adaptor from the Total Plus Pak(®) (Alcon, Fort Worth, USA) was used to join the microcannula and silicone vacuum tube connected to an external vacuum pump. Main outcome measures were mean removal time, changes of intraocular pressure (IOP) and visual acuity, and intraoperative and postoperative complications., Results: Mean removal time (min) was 1.49±0.43 for 1000 cSt and 7.12±1.27 for 5700 cSt. The IOP was 18.57±7.48 mm Hg at baseline, 11.68±4.55 mm Hg at day 1 postoperatively (P<0.001), and 15.95±4.92, 16.82±3.81, 17.41±3.50, and 17.09±3.01 mm Hg after one week, one month, three months, and six months, respectively. All patients showed improved or stabilized visual acuity. There was no occurrence of intraoperative or postoperative complications during the follow up period., Conclusion: This technique for active removal of silicone oil through a 23-gauge cannula using an external vacuum pump is fast, effective, and safe as well as economical for silicone oil with both low and high viscosity in all eyes with pseudophakia, aphakia, or phakia.

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

We report a case of Valsalva retinopathy associated with esophagogastroduodenoscopy (EGD) under propofol sedation. A 43-year-old woman who had no previous history of systemic or ocular disease presented with a complaint of decreased vision in her left eye, which developed one day after EGD under propofol sedation. According to the referring physician, the patient had experienced multiple sustained Valsalva maneuvers during EGD. The fundus examination of the left eye showed a large preretinal hemorrhage surrounded by multiple small retinal hemorrhages in the posterior pole. One month later, fundus examination revealed a floating organized vitreous hemorrhage. The pars plana vitrectomy was performed to treat persistent vitreous hemorrhage. One month after vitrectomy, fundus examination showed normal retina and the patient's vision recovered to 20/20. Valsalva maneuver can occur during EGD under sedation, and Valsalva retinopathy should be considered as a possible cause. Valsalva retinopathy should be included in the differential diagnosis when a patient complains of blurred vision following EGD.

Purpose: To determine whether genetic factors that influence age-related macular degeneration (AMD) have an early pharmacogenetic effect on treating exudative AMD with ranibizumab in a Korean population., Methods: A retrospective study of 102 patients (70 with typical neovascular AMD and 32 with polypoidal choroidal vasculopathy) with exudative AMD treated with intravitreal ranibizumab monotherapy was conducted. Optical coherence tomography, fluorescein, and indocyanine green angiography were taken at the baseline. The best-corrected visual acuity (BCVA) and the central subfield macular thickness (CSMT) were recorded at the baseline and at each monthly visit. The genotypes of the polymorphisms in the known AMD susceptibility loci (CFH, AMRS2, HTRA1, VEGFA, and KDR) were determined, and association between their frequencies and the changes in the BCVA and the CSMT were evaluated., Results: The mean baseline visual acuity was 0.96 ± 0.59 logMAR (approximately 20/200 in the Snellen equivalent), and the mean number of injections was 3.87 before the month 6 visit. No association was observed between the change in BCVA and each genotype. For the changes in the CSMT, a significant difference was observed only with the VEGF-A (rs833069) gene. The decrease in the CSMT at month 3 for the major allele homozygote AA genotype, the heterozygote AG genotype, and the risk allele homozygote GG genotype was 25.66 ± 85.40, 86.93 ± 92.31, and 85.30 ± 105.30 μm, respectively (p=0.012, p=0.044, and p=0.002 for AG, GG, and combined AG or GG genotype, respectively, compared to the AA genotype). This trend was maintained until month 6., Conclusions: The VEGF-A (rs833069) polymorphism showed a significant association with the anatomic response to intravitreal ranibizumab. No significant difference was found between the genotype of the potential risk polymorphism for development of AMD and the early visual improvement after intravitreal ranibizumab.

Porcine reproductive and respiratory syndrome virus (PRRSV) shows highly restricted cell tropism and targets subpopulations of differentiated macrophages such as porcine alveolar macrophages (PAM) in the natural host. Although primary PAM cells would be ideal for in vitro virus production, they are not only difficult and expensive for establishment but cannot be frozen reliably for long-term storage and use. Apart from PAM cells, African green monkey kidney derived Marc-145 cells are used commonly for virus propagation. However, concerns have been raised regarding a possible modification of specific epitopes associated with virus neutralization because of distinct virus entry between PAM and Marc-145 cells. In order to overcome these problems, the present study was aimed to generate immortalized porcine monocyte/macrophage cell lines and to evaluate their potential for PRRSV production. Primary PAM cells were transfected stably with the human telomerase reverse transcriptase (hTERT) cDNA by a retrovirus vector so that constitutive expression of the hTERT protein allows cells to proliferate indefinitely. The newly immortalized PAM clones were shown to exert functional telomerase activity, indicating sustained expression of hTERT. In addition, telomerase-immortalization of PAMs did not affect expression levels of the native CD163 receptor on their surface. It was further demonstrated that these continuous PAM cell lines are fully permissive for the efficient growth of both type 1 and 2 PRRSV strains. The findings suggest that the hTERT-immortalized PAM cell lines can enable us to facilitate the continued use of PAMs for virus isolation and production and to provide a promising tool for viral pathogenesis and immune function studies., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Porcine reproductive and respiratory syndrome virus (PRRSV) infection appears to elicit a weak innate immune response suppressing type 1 interferon (IFN) production. Recent studies have revealed that several nonstructural proteins encoded by the PRRSV genome independently antagonize the type 1 IFN system. The present study sought to identify the structural proteins that possess the immune evasion properties in immortalized porcine alveolar macrophages (PAM). Each structural protein gene was stably expressed in a porcine monocyte-derived macrophage cell line, PAM-pCD163, and tested for its potential to inhibit IFN-β induction. We then focused on the nucleocapsid (N) protein, which has a strong inhibitory effect on dsRNA-induced IFN-β production. Upon dsRNA stimulation, IFN-β production was shown to decrease proportionally with increasing levels of N expression. Furthermore, the PRRSV N protein was found to down-regulate IFN-dependent gene production by dsRNA. Taken together, these results indicate the ability of N to modulate the dsRNA-mediated IFN induction pathways. In addition, the N protein significantly interfered with dsRNA-induced phosphorylation and nuclear translocation of IRF3. Our data suggest that the PRRSV N protein is a responsible component, independent of other nonstructural elements, for evading the IFN response by antagonizing IRF3 activation.

Purpose: To evaluate the association of the lysyl oxidase-like 1 (LOXL1) single nucleotide polymorphisms (SNPs) in the Korean population with exfoliation syndrome (XFS) and to investigate the association between the SNPs and phenotypes of XFS., Methods: Eighty-nine unrelated patients with XFS and 146 unrelated control subjects were recruited. LOXL1 SNPs, rs1048661, rs3825942, and rs2165241, were genotyped by direct DNA sequencing. Association between cases and controls was analyzed and phenotypic features of XFS were compared in terms of the SNPs., Results: The three SNPs were found to be significantly associated with XFS. After adjusting for rs3825942, rs2165241, and other factors influencing the prevalence of XFS, only rs1048661 among three SNPs remained significant (95% confidence interval=4.11-35.78, p=6.11×10(-6)). T allele and TT genotype of rs1048661 and C allele and CC genotype of rs2165241 were associated with XFS, showing risk alleles and genotypes opposite to those reported in Caucasians. In the haplotype analysis, T-G-C was the only risk haplotype (p=3.35×10(-12)), which was not associated with XFS in Caucasians. No significant differences were noted in the allele and genotype frequencies depending on phenotypic features of XFS., Conclusions: Three LOXL1 SNPs are associated with XFS in the Korean population. Risk alleles and genotypes of rs1048661 and rs2165241 in Korean have a similar pattern with those of East Asians, including Japanese and Northern Chinese, while they have a different pattern from those of Caucasians.

We present a case of bilateral serous retinal detachment (SRD) as a presenting sign of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). A 45-year-old woman presented with decreased vision and was found to have bilateral serous retinal detachment. Peripheral blood smears revealed leukocytosis of 53.9x10(3)/microL with 64.6% lymphoblasts. A bone marrow aspirate revealed the presence of lymphoblasts. Cytogenetic and molecular genetic analysis detected a reciprocal translocation between chromosome 9 and 22, t(9;22) (q34;q11). A diagnosis of Ph(+) ALL was made. Following systemic chemotherapy, the bilateral SRD resolved completely with full recovery of vision. The sudden appearance of SRD should raise suspicion for leukemia. Prompt recognition of this disease is important for early systemic treatment and restoration of visual function.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a leading cause of significant economic losses in the pig industry worldwide. PRRSV infects preferentially porcine alveolar macrophages (PAMs) and subsequently utilizes the host cell biosynthetic machinery for its own replication. To date, a number of studies have been conducted to investigate compensatory changes of cellular gene expression of PAMs upon PRRSV infection. However, very little information exists about differential cellular protein expression of the natural target cells regulated by each viral protein. This study was therefore designed to examine the dynamics of host protein expression of continuous PAM cells by the PRRSV nucleocapsid (N) protein that is the most abundant and multifunctional viral component. We first established sublines of PAM cells to stably express the PRRSV N protein and assessed alterations in cellular protein productions of N-expressing PAM (PAM-pCD163-N) cells at different time courses by the use of proteomic analysis. A total of 23 protein spots were initially found to be differentially expressed in PAM-pCD163-N cells compared with normal PAM cells by high-resolution two-dimensional gel electrophoresis (2DE). Of these spots, 15 protein spots with statistically significant alteration, including 4 up-regulated and 11 down-regulated protein spots, were picked out for subsequent protein identification by peptide mass fingerprinting after matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS). The altered cellular proteins identified in this study were classified into the functions involved in a variety of cellular processes such as cell division, metabolism, inflammation response, stress response, ubiquitin-proteasome pathway, protein folding and synthesis, and transportation. Notably, heat shock 27kDa protein (HSP27) was found to be up-regulated in PAM-pCD163-N cells. The proteomics data will provide insights into the specific cellular response to the N protein during PRRSV infection.

Despite global efforts to control porcine reproductive and respiratory syndrome virus (PRRSV) infection, the virus continues to cause economic problems in the swine industry worldwide. In this study, we attempted to generate and characterize a panel of stable BHK cell lines that constitutively express the nucleocapsid (N) protein of type 1 or type 2 PRRSV. The established BHK cell lines were found to react well with N-specific antibodies as well as the hyperimmune serum of pigs raised against each genotype of PRRSV. Taken together, the data implicate a potential usefulness for the newly generated stable cell lines as a diagnostic reagent for PRRSV serology.

Background/aims: To provide an insight into the learning curve associated with scleral buckling surgery for an ophthalmologist on a fellowship course and to evaluate risk factors affecting outcomes during this period., Methods: Retrospective data were collected on 97 consecutive scleral buckling procedures (divided into 3 consecutive groups) performed by one surgeon (W.C.) beginning his first fellowship year. We evaluated the anatomic results, operative times and complications, and sought to identify risk factors of anatomic failure., Results: The single-operation success rate was 71.9% (23 of 32 eyes) in the first group, which was lower than 87.5% (28 of 32 eyes) in the second and 84.8% (28 of 33 eyes) in the third. The operative time was 106.3 min in the first, which is longer than 86.5 min in the second and 73.8 min in the third group. Factors predictive of unfavorable anatomic outcome were multiple breaks and multiple buckling procedures in the first 32 cases, and multiple breaks and breaks located posterior to the equator in the latter 65., Conclusion: Surgical experience of approximately 30 cases was required to achieve stable clinical results. Thus, a retinal surgeon at the beginning of his career may increase his success rate by careful case selection avoiding high-risk groups until he reaches the level of experience indicated by the learning curve., ((c) 2009 S. Karger AG, Basel.)

We report three cases of neovascular glaucoma secondary to central retinal artery occlusion (CRAO) which were effectively managed with intravitreal bevacizumab (IVB) followed by panretinal photocoagulation (PRP). Neovascular glaucoma without peripheral anterior synechiae developed between one and five weeks following CRAO onset. All patients received 0.75 mg (0.03 ml) IVB. In all patients, complete regression of the iris and anterior chamber angle neovascularization was confirmed within one week. PRP was applied two weeks after the injection. The follow-up period was four to seven months (average, five months). Intraocular pressure was controlled in all patients using topical antiglaucoma medications alone. However, one patient experienced a recurrence of neovascularization three months after the initial combination treatment. This patient received another IVB injection and additional PRP, and the recurrent neovascularization resolved. There were no local or systemic adverse events in any patients. Therefore, intravitreal bevacizumab may be an effective adjunct in the treatment of neovascular glaucoma associated with CRAO.

We report 3 cases of circumscribed choroidal hemangioma (CCH) effectively managed with intravitreal bevacizumab. One patient (case 1) who had recurrent CCH (1.6 mm in thickness) with prior laser photocoagulation was treated with intravitreal bevacizumab alone. Two patients (case 2 and 3) who had CCH (2.4 mm and 2.2 mm in thickness, respectively) with recent visual impairment were treated with bevacizumab followed by photodynamic therapy (PDT). Ophthalmic evaluations included visual acuity, ophthalmoscopic examination, fluorescein angiography, ultrasonography, and optical coherence tomography. Patients were followed up for 6-9 months. After therapy, all patients showed improved visual acuity due to complete resorption of subretinal fluid and macular edema. Ultrasonography demonstrated a reduction of the thickness of CCH in case 1 and complete regression of the lesions in case 2 and 3. No patient showed tumor recurrence. Intravitreal bevacizumab, alone or in combination therapy with PDT, may be a useful alternative for the treatment of symptomatic CCH with subretinal fluid.