[Show abstract][Hide abstract] ABSTRACT: MiRNAs are small noncoding RNAs that have been implicated in tumor development. They regulate target gene expression either by mRNA degradation or by translation repression. Activation of β-catenin has been linked to pterygium progression. Here, we hypothesize that β-catenin-associated miRNA, miRNA-221, and downstream p27Kip1 gene expression are correlated with the pathogenesis of pterygium.
[Show abstract][Hide abstract] ABSTRACT: Vascular endothelial growth factor (VEGF) gene expression has been linked to cancer progression. Here we hypothesise that the polymorphism and protein expression of VEGF are correlated with the pathogenesis and therapy response of pterygium.
60 pterygial and 121 normal conjunctival samples were collected to determine the genotypes and protein expression of VEGF. Primary pterygium cells (PECs) were used to confirm the effect of the VEGF polymorphism on the angiogenesis of pterygium.
48 (83.3%) pterygial specimens tested positive for VEGF protein expression, which was significantly higher than in the control groups (16.7%, p<0.0001). The frequency of the 936 C>T variant, but not the -2578C>A variant, was significantly higher in the pterygium group compared with the control group. VEGF protein expression was significantly higher in the 936 C/C group than in the 936 C/T and T/T groups (p=0.001). The results of our cell model showed that PECs with the C/C genotype had a higher angiogenesis ability and higher response to the antiangiogenesis drug bevacizumab than cells with the C/T and T/T genotypes.
We suggest that VEGF could be used as a target for pterygium therapy in patients with the 936C>T genotype.
The British journal of ophthalmology 10/2013; · 2.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: To describe a scleral indentation technique to enhance donor adherence in Descemet's stripping and automated endothelial keratoplasty (DSAEK) in patients with abnormal anterior segment. METHODS: In patients with visual potential, we performed transscleral fixation of a foldable intraocular lens (IOL) and DSAEK. In patients only for pain relief, we performed DSAEK without IOL implantation. During air tamponade, we injected only a medium air bubble instead of big bubble into anterior chamber and used scleral indentation technique as an aid. The position of the grafts was checked by the slit lamp and anterior segment optical coherence tomography (AS-OCT). RESULTS: Five eyes of five patients of aphakic bullous keratopathy (ABK) or pseudophakic bullous keratopathy (PBK) with anterior chamber IOL (AC IOL) were included in this non-comparative interventional case series. The grafts attached well in all patients without any graft dislocation intraoperatively and during the follow-up period. There was no pupillary block or peripheral anterior synechiae postoperatively. CONCLUSIONS: Scleral indentation technique with or without transscleral fixation of a foldable IOL in DSAEK can facilitate the air tamponade and enhance the donor adherence in certain anterior segment abnormities.
Albrecht von Graæes Archiv für Ophthalmologie 01/2013; · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
To evaluate visual acuity (VA), refractive outcome, endothelial cell loss rate and complications of Descemet's stripping and automated endothelial keratoplasty (DSAEK) combined with phacoemulsification and intraocular lens (IOL) implantation in patients with coexisting corneal endothelial dysfunction and cataracts.
Seventeen patients underwent phacoemulsification and posterior chamber IOL implantationthrough temporal corneal incision, followed by DSAEK. The selection of IOL power was predicted by preoperative lens power calculations of fellow eye plus 0.5 to 1.0 diopters (D).
There were five cases of laser iridotomy induced corneal dysfunction, four cases of Fuch's dystrophy, three cases of cytomegalovirus (CMV) endotheliitis, three cases of iridocorneal endothelial (ICE) syndrome, one case of herpes simplex virus (HSV) endotheliitis, and one case with an unknown cause. The BSCVAs were all under 0.2 preoperatively, and the average BSCVA was 0.3 postoperatively. The postoperative spherical equivalent (SE) refractive error was −0.11 D on an average. The endothelial cell loss rate was −36.86% at 6 months and −38.60% at 12 months. There was one case of graft rejection at 6 months, and one case of primary graft failure. Complications such as donor detachment, pupillary block, donor graft folds, epithelial ingrowth, or interface scar did not occur.
This case series of DSAEK combined with phacoemulsification and IOL implantation suggests that the procedure provides rapid visual rehabilitation and allows the selection of an appropriate IOL.
Taiwan Journal of Ophthalmology. 01/2013; 3(2):54–57.
[Show abstract][Hide abstract] ABSTRACT: Population-based cohort study on the risk of anxiety and depression in patients with blepharitis is limited. This study evaluated whether blepharitis patients are at a higher risk of anxiety and depression.
A retrospective cohort study.
We used the universal insurance claims data from 1997 to 2010 in Taiwan to identify annually patients with newly diagnosed blepharitis (N = 9764) and without the disease (N = 39056). Incidences, rate ratios (IRR) and hazard ratios (HR) of anxiety and depression were measured for both cohorts by baseline demographic characteristics and comorbidities until the end of 2010.
Compared with the non-blepharitis cohort, the blepharitis cohort had higher incidence of anxiety (15.9 vs. 9.5 per 1000 person-years), with an adjusted HR of 1.58 (95% confidence interval (CI) = 1.46-1.70). The incidence of depression was also higher in the blepharitis cohort (7.66 vs. 5.05 per 1000 person-years), with an adjusted HR of 1.42 (95% CI = 1.28-1.58). The blepharitis cohort to the non-blepharitis cohort IRR decreased from 1.73 in the first quartile to 1.32 in the 4(th) quartile for anxiety, and from 1.67 to 1.29 for depression.
Patients with blepharitis are at elevated risks of anxiety and depression. The risk is higher in earlier period after the diagnosis of blepharitis, and declines by time, but remains significantly higher for those with blepharitis than those without blepharitis.
PLoS ONE 01/2013; 8(12):e83335. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose. This study evaluated the clinical outcomes of a combined method of scraping corneal epithelium, coagulating vessels, and subconjunctival bevacizumab in Descemet stripping automated endothelial keratoplasty (DSAEK) for bullous keratopathy with corneal neovascularization (NV). Methods. The study included patients with bullous keratopathy undergoing DSAEK. Indications for DSAEK were advanced pseudophakic bullous keratopathy with superficial and deep corneal vascularization and failed corneal grafts. Patients were treated by scraping the corneal epithelium and lightly coagulating the corneal superficial stromal NV and the feeding vessels in the sclera, with a subconjunctival bevacizumab injection at the end of surgery. Subconjunctival and perilimbal bevacizumab dose of 2.5 mg/0.1 mL/affected quadrant was injected at the site of NV in each patient at the end of surgery. One or 2 injections were applied. At each visit, a full eye examination with photographic documentation was performed. Mean follow-up period was 32 (24-36) months. Results. Eight eyes of 8 patients with high-risk corneal transplantation and corneal NV were included in this noncomparative interventional case series. The original corneal NV disappeared in all patients immediately after surgery. No patient in the series had recurrent corneal NV or rejection during at least 24 months of follow-up. Conclusions. The combination of scraping, coagulating, and bevacizumab injection in DSAEK is an effective method to treat corneal NV in corneal transplantation for bullous keratopathy.
European journal of ophthalmology 11/2012; · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study is to evaluate whether daily clinic visits for conjunctivitis are associated with the ambient environment in urban and rural areas of Taiwan. The incidences of acute and chronic conjunctivitis (International Classification of Disease 9 Clinical Modification 372.0 and 372.1) in two urban cities and two rural counties and their relative risks (RRs) are associated with air pollutants (nitrogen oxides (NOx), sulfur dioxide, ozone, and particulate matter <10 μm in aerodynamic diameter) and/or weather statuses were assessed from the insurance reimbursement claims of a representative 1 million people from 2000 to 2007. The patients resided in rural counties were approximately eight time more likely to have acute complains and >1.3 time more likely to have chronic complaints than the patients lived in the capital, Taipei. Per 10 °C increment of the daily average temperature increased the risk of acute conjunctivitis and chronic conjunctivitis with RRs of 1.06 (95% confidence interval (CI): 1.03-1.09) and 1.05 (95% CI: 1.04-1.07), respectively. A 10-p.p.b. increase in NOx concentration also increased the risk of acute conjunctivitis (RR=1.03, 95% CI: 1.02-1.04) and chronic conjunctivitis (RR=1.06, 95% CI: 1.05-1.06). Residents in rural counties, females, the elderly, and children have higher risk of conjunctivitis. Ambient temperature and NOx concentration can cause greater significant risks on the diseases.
Journal of Exposure Science and Environmental Epidemiology 06/2012; 22(5):533-8. · 3.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A thymine/cytosine point mutation in the MSP I restriction site of cytochrome P450 1A1 (CYP1A1) has been linked to susceptibility to smoking-related cancers and is reported to result in increased enzyme activity. Therefore, we sought to determine whether allelic variation of CYP1A1 is associated with protein expression and protein activity in pterygium.
We collected 150 pterygium samples and 50 normal conjunctiva samples, which served as controls. DNA samples were extracted from blood cells and then subjected to real-time ploymerase chain reaction (PCR) to determine CYP1A1 genotype. CYP1A1 protein expression was determined by immunohistochemical staining with a monoclonal antibody for CYP1A1. Pterygium epithelial cells (PECs), cultured in a serum-free culture medium, real-time PCR, western blot and enzyme-linked immunosorbent assay (ELISA) were used to understand the effect of CYP1A1 allelic variation in protein expression and activity.
Forty-eight (33.3%) pterygium specimens tested positive for CYP1A1 protein expression. CYP1A1 protein expression was significantly greater in the pterygium group than in the control group (p<0.0001). In addition, CYP1A1 protein expression was associated with allelic variation. CYP1A1 protein expression was significantly greater in the m2/m2 group than in the m1/m1and m1/m2 groups (p=0.006). In the cell model, CYP1A1 protein expression and b[a]P 7,8-diol 9,10-epoxide (BPDE)-like DNA adducts increased in CYP1A1 m2/m2 (genotype T/T) PEC cells as compared with m1/m2 (genotype C/T) and m1/m1 (genotype C/C) cells.
CYP1A1 expression in pterygium correlates with allelic variation and can be used as an independent risk marker.
[Show abstract][Hide abstract] ABSTRACT: PurposeThis study investigated clinical outcomes of the combined method of scraping, coagulation, and subconjunctival bevacizumab for the treatment of corneal neovascularization (NV) in penetrating keratoplasty (PKP).Methods
This study included patients undergoing PKP who were diagnosed with bullous keratopathy with dense subepithelial scarring that was not suitable for Descemet’s stripping automated endothelial keratoplasty. Corneal NV was treated by scraping the corneal epithelium and lightly coagulating the superficial corneal stromal NV combined with subconjunctival bevacizumab injection at the end of surgery. Patients without corneal NV were used as the control group.ResultsThere were six patients with vascularized corneas in the study group and three patients without vascularized corneas in the control group. The original corneal NV in the study group disappeared in all patients after surgery. Three of the six (50%) study patients experienced recurrent corneal NV. One of the three (33%) control patients developed corneal NV. These patients had no corneal NV recurrences over the next 6 months after repeat treatment. In both groups, no graft failure or chronic epithelial defects occurred.Conclusion
The combination of scraping the corneal epithelium, coagulating the superficial corneal stromal NV and the feeding vessels in the sclera after peritomy, and subconjunctival bevacizumab injection is an effective method to treat corneal NV in corneal transplantation for bullous keratopathy.
Taiwan Journal of Ophthalmology. 12/2011; 1(1):21–24.
[Show abstract][Hide abstract] ABSTRACT: To describe an atypical case of cytomegalovirus (CMV) endotheliitis in a 74-year-old man who presented with chronic corneal edema without keratic precipitates (KPs) and intraocular pressure (IOP) elevation.
A complete ophthalmologic examination was performed. Polymerase chain reaction was used to test for herpes simplex virus, varicella zoster virus, and CMV DNA in aqueous humor samples to rule out viral endotheliitis.
Severe bullous keratopathy was found in the temporal part of the cornea without KPs or elevated IOP. CMV DNA was detected. Corneal edema subsided with oral valganciclovior.
CMV endotheliitis may present as corneal edema that lacks typical features, such as KPs or elevated IOP.
Ocular immunology and inflammation 10/2010; 19(1):69-71. · 0.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE. The migration and invasion of tumor cells correlate with the interaction between MMP and TIMP. Therefore, the purpose of this study was to determine the role of MMP-9, MMP-10, and TIMPs in pterygium formation and progression. METHODS. MMP-9, MMP-10, and TIMP proteins were studied using immunohistochemistry on 82 pterygial specimens and 30 normal conjunctivas. Pterygium epithelial cells (PECs), cultured in a serum-free culture medium, and siRNA were used to knock down TIMP gene expression to understand the role of TIMP in pterygium invasion. RESULTS. Among the 82 pterygial samples, 29 specimens (35.4%) were positive for MMP-9 expression, 28 were positive for MMP-10 (34.1%), and 59 were positive for TIMP1 (72.0%). Staining for MMPs was limited to the cytoplasm of the epithelial layer. The TIMP staining was detected in the pterygium epithelium, fibroblasts and corneal epithelium. In the cell model, cell invasion and migration ability increased in TIMP knockdown PECs compared with the parental control. CONCLUSIONS. MMP-9 and MMP-10 may each play a role in pterygium formation, and TIMPs may contribute to pterygium invasion inhibition.
[Show abstract][Hide abstract] ABSTRACT: Pterygium is an ultraviolet (UV) related disease. UV radiation can produce DNA damage, which is repaired by the DNA repair systems. Among the DNA repair systems, the base excision repair (BER) and nucleotide excision repair (NER) systems are the major ones involved in repairing UV-induced DNA damage; X-ray repair cross complementary 1 (XRCC1) and human 8-oxoguanine DNA glycosylase 1 (hOGG1) are two BER genes, and xeroderma pigmentosum group A (XPA) and xeroderma pigmentosum group D (XPD) are two NER genes. Polymorphisms of these genes are associated with the differences in their repair DNA damage capacity, and they modulate the susceptibility to cancer. Because the polymorphism of hOGG1 was reported to be associated with pterygium, it is logical to assume the correlation between XRCC1, XPA, and XPD polymorphisms and pterygium formation.
One hundred and twenty-seven pterygium patients and 103 volunteers without pterygium were enrolled in this study. Polymerase chain reaction based analysis was used to resolve the XRCC1 codon 107, 194, 280, and 399; XPA A23G; XPA codon 228; and XPD codon 751 polymorphisms.
There were significant differences in the frequency of genotypes and alleles of XRCC1 codon 194 and 399 polymorphisms between the groups. In codon 194, individuals who carried at least 1 Trp allele had a decreased risk of developing pterygium compared to those who carried the Arg/Arg wild-type genotype (odds ratio [OR]=0.58; 95% CI: 0.34-0.98). In codon 399, individuals who carried at least 1 Gln allele had a threefold increased risk of developing pterygium compared to those who carried the Arg/Arg wild-type genotype (OR=3.06; 95% CI: 1.78-5.26). There were no significant differences in the frequency of the genotypes and alleles of XRCC1 codon 107 and 280, XPA A23G, and XPD codon 751 polymorphisms between the groups. The XPA codon 228 polymorphism was not detected in any of the cases or controls.
The XRCC1 codon 194 polymorphism causes a decreased risk of developing pterygium, but the codon 399 polymorphism increases the risk. There is no correlation between pterygium and XRCC1 codon 107 and 280, XPA A23G, and XPD codon 751 polymorphisms.
[Show abstract][Hide abstract] ABSTRACT: Our recent reports indicated that the molecular changes of pterygia are similar to tumor cells. We believe that pterygia may have a similar mechanism in oncogenesis. Many studies have revealed that E-cadherin associated protein expression decreases in many tumors and pterygia. E-cadherin may be a marker for both tumor metastasis and prognosis. However, no studies have examined the reason for E-cadherin protein inactivation in pterygia. Therefore, this study aimed to analyze the association of E-cadherin promoter hypermethylation with protein inactivation in pterygial tissues.
E-cadherin methylation-status and the expression of E-cadherin and beta-catenin protein were studied using methylation-specific PCR and immunohistochemistry, respectively, on 120 pterygial specimens and 30 normal conjunctivas.
Hypermethylation of E-cadherin gene promoter was detected in 32 (26.7%) of the 120 pterygial specimens. A total of 79 (65.8%) pterygial specimens tested positive for E-cadherin protein expression and 41 (34.2%) specimens tested negative. The E-cadherin staining was limited to the membrane of the epithelial layer. There was a reverse correlation between E-cadherin gene promoter hypermethylation and E-cadherin protein expression (p<0.0001). Aberrant localization of beta-catenin was higher in the E-cadherin negative group than in E-cadherin positive group.
Our study demonstrates E-cadherin gene promoter hypermethylation were associated with low or absent expression of E-cadherin. Moreover, loss of E-cadherin protein may contribute to aberrant localization of beta-catenin. These data provide evidence that methylation exists in pterygia and may play a role in their development.
[Show abstract][Hide abstract] ABSTRACT: The Wnt (Wg/Wnt) signaling cascade plays an important role in tumorigenesis. Our previous report indicated that aberrant localization of β-catenin proteins was a feature of pterygia. Therefore, this study aimed to analyze the association of β-catenin protein and expression of a downstream gene, cyclin D1, in pterygial tissues.
Using immunohistochemistry, β-catenin and cyclin D1 protein expression was studied, in 150 pterygial specimens and 30 normal conjunctivas.
Seventy-three (48.7%) and 60 (40.0%) pterygial specimens tested positive for β-catenin and cyclin D1 protein expression, respectively. Cyclin D1protein expression was significantly higher in β-catenin-nuclear/cytoplasmic positive groups than in β-catenin membrane positive and negative groups (p < 0.0001). In addition, cyclin D1 expression was significantly higher in the fleshy group than in the atrophic and intermediate groups (p = 0.006).
Our study demonstrated that β-catenin expressed in nuclei/cytoplasm increases cyclinD1 protein expression, which invokes pterygial cell proliferation.
[Show abstract][Hide abstract] ABSTRACT: Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), an ultimate metabolite of benzo[a]pyrene, attacks deoxyguanosine to form a BPDE-N2-dG adduct resulting in p53 mutations. Both cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) have been demonstrated to be involved in the metabolism of polycyclic aromatic hydrocarbons. The relationship between BPDE-like DNA adduct levels and CYP1A1 and GSTM1 gene polymorphisms in pterygium is not clear. Therefore, BPDE-like DNA adducts and CYP1A1 and GSTM1 polymorphisms were detected in this study to provide more molecular evidence to understand the cause of BPDE-like DNA adduct formation in pterygium.
In this study, immunohistochemical staining using a polyclonal antibody on BPDE-like DNA adducts was performed on 103 pterygial specimens. For the analysis of CYP1A1 and GSTM1 polymorphisms, DNA samples were extracted from epithelial cells and then subjected to restriction fragment length polymorphism (RFLP) and polymerase chain reaction (PCR) for the determination of mutation and genotype of CYP1A1 and GSTM1.
BPDE-like DNA adducts were detected in 33.0% (34/103) of the pterygium samples. The differences in DNA adduct levels were associated with the genetic polymorphisms of CYP1A1 but not GSTM1. Additionally, the risk of BPDE-like DNA adduct formation for patients with CYP1A1 m1/m2 (C/T) andm2/m2 (T/T) was 9.675 fold higher than that of patients with CYP1A1 m1/m1 (C/C) types (p=0.001, 95% Confidence Interval 2.451-38.185).
Our data provide evidence that the BPDE-like DNA adduct formation in pterygium samples was associated with CYP1A1 polymorphisms.
[Show abstract][Hide abstract] ABSTRACT: To describe a rare case of early-onset Candida parapsilosis infection after laser in situ keratomileusis (LASIK) and review the published reports of post-LASIK fungal infections.
A 32-year-old woman presented with interface infiltration in the central interface in the right eye 2 days after LASIK surgery. The right eye flap was lifted, and the opacities were scraped. Two days later, a 3- x 3-mm-dense oval opacity and diffuse hazes were noted. Surgical intervention was arranged because of suspicion of interface infectious keratitis.
After an apparent post-LASIK keratitis with related interface inflammation failed to respond to medical therapy, corneal culture results were positive for C. parapsilosis 2 weeks 6 days after presentation. The patient was started on topical drops of amphotericin B 0.15% every hour after the smear showed the presence of yeast. The opacities decreased, and the topical antifungal drops were tapered. One month later, her uncorrected visual acuity recovered to 20/20.
Candida parapsilosis interface keratitis after LASIK may occur in the early phase. Early diagnosis and proper treatment can result in good outcome.