Increased oxidative DNA damage, lipid peroxidation, and reactive oxygen species in cultured orbital fibroblasts from patients with Graves' ophthalmopathy: evidence that oxidative stress has a role in this disorder.

PURPOSE: We investigated the oxidative stress in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with Graves' ophthalmopathy (GO). METHODS: The content of 8-hydroxy 2'-deoxyguanosine (8-OHdG), an important biomarker of oxidative DNA damage, was measured in orbital fibroadipose tissues and cultured orbital fibroblasts from patients with GO and compared with age-matched normal controls. A product of lipid peroxidation, malondialdehyde (MDA), and intracellular reactive oxygen species (ROS) in cultured orbital fibroblasts was also determined. RESULTS: There was no significant difference in the 8-OHdG content of orbital fibroadipose tissues between patients with GO and age-matched normal controls (P=0.074). However, the levels of 8-OHdG and MDA in GO orbital fibroblasts were significantly higher than those of normal controls (P=0.0026 and P<0.001, respectively). In addition, GO orbital fibroblasts had higher contents of superoxide anions and hydrogen peroxide compared with those of normal controls (P=0.0133 and 0.0025, respectively). CONCLUSIONS: Orbital fibroblasts represent the most abundant cell type among orbital connective tissues and exhibit great differences in their phenotypes. Increased oxidative DNA damage and lipid peroxidation, as well as higher intracellular ROS levels in GO orbital fibroblasts may have a role in the pathogenesis of GO.

Oxidative stress in patients with Graves' ophthalmopathy: relationship between oxidative DNA damage and clinical evolution.

PURPOSE: To evaluate the relationship between oxidative stress and clinical evolution in patients with Graves' ophthalmopathy (GO). METHODS: Thirty-one euthyroid GO patients and 25 healthy subjects participated in this study. Oxidative DNA damage was assessed by determination of the 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in urine by ELISA. The relationship of oxidative DNA damage to the clinical evolutions of GO, especially the smoking status, clinical activity scores (CAS), and ophthalmopathy index was examined. RESULTS: The mean 8-OHdG was significantly higher in GO patients than that of normal controls (12.6+/-5.7 vs 6.7+/-2.5 ng/mg creatinine, P<0.001). Smokers had significant higher 8-OHdG than did never smokers in GO patients (P=0.029), but not in healthy controls (P=0.374). Among GO patients, only CAS remained significantly correlated with 8-OHdG (P=0.001) after adjusting for age, sex, disease duration, the status of antithyroid drug and smoking, and thyroid-stimulating hormone level. Patients with active GO (CAS>3) had higher 8-OHdG than did the patients with CAS

Exophthalmos of patients with Graves' disease in Chinese of Taiwan.

PURPOSE: To determine the exophthalmos measurements in patients with Graves' disease (GD) and to compare with those of normal subjects among the Chinese of Taiwan. METHODS: Hertel's exophthalmometry were performed in 163 consecutive adult GD patients and 419 normal subjects. The values of exophthalmos, asymmetry, and the distance between lateral orbital rims (base) were evaluated. RESULTS: There was a significant difference between GD and normal adults for exophthalmos and asymmetry, with GD patients demonstrating a mean exophthalmos of 18.32 mm and asymmetry of 0.93 mm as compared with 13.91 and 0.55 mm for normal subjects (P<0.001). The mean value of base for GD adults (106.52 mm) is slightly greater than normal subjects (105.82 mm). There was no gender difference in exophthalmometric value or asymmetry in each group. A total of 79 (48.5%) GD patients had exophthalmos greater than the upper limit of normal Chinese in Taiwan (18.6 mm). Asymmetry over 2 mm was observed in 11 (6.7%) patients with GD but in none of the normal subjects. CONCLUSIONS: GD patients have significant exophthalmos and asymmetry compared to normal subjects. In comparison with previous studies, exophthalmos values for Chinese in Taiwan tend to be lower than those of Caucasians and black-American people, but are close to those of Korean, Japanese, Iranian, Indian, and Asian-American people. Adequate adjustment of normal and abnormal values of exophthalmos according to individual differences is important for the diagnosis of orbital morbidity and management of thyroid associated orbitopathy.

Pulsatile ocular blood flow change after treatment with systemic steroid in patients with Graves' ophthalmopathy.

PURPOSE: Our previous study has demonstrated an impairment of pulsatile ocular blood flow (POBF) in patients with Graves'ophthalmopathy (GO). Here we further evaluate the haemodynamic change in GO patients after systemic steroid. METHODS: In a prospective, interventional, consecutive clinical case series, all patients with active and moderately severe GO who underwent systemic steroid treatment were evaluated. The change of POBF and the clinical activity and severity of the disease were assessed. RESULTS: In total, 11 patients underwent intravenous methylprednisolone pulse therapy followed by 2-month oral prednisolone therapy. POBF improved from a mean value of 476.5 to 614.7 microl/min (P<0.001) after treatment. Likewise, the mean clinical activity score reduced from 4.8 to 1.6. However, systemic steroid had less effect on the severity of GO. It also revealed that there is a greater improvement of POBF in those with more clinical activity score (>4) at the onset. CONCLUSIONS: Following treatment with systemic steroid we have demonstrated a significant improvement in POBF in patients with GO.

Increased oxidative DNA damage, 8-hydroxydeoxy- guanosine, in human pterygium.

PURPOSE: Chronic exposure to ultraviolet (UV) light is a widely accepted aetiological factor in the development of pterygium. UV radiation may induce production of reactive oxygen species via photosensitized oxidation, thus causing oxidative damage. This study was conducted to test the hypothesis that oxidative damage to DNA is increased in pterygium. METHODS: Immunohistochemical analysis employing a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a ubiquitous maker of oxidative stress, was performed in three patients with primary pterygium. The levels of 8-OHdG in DNA isolated from the other 29 pterygium specimens and their adjacent normal conjunctival tissues were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: Immunohistochemistry of 8-OHdG showed a distinct pattern of more extensive and intense staining in the nuclei of pterygium tissue compared with that in their adjacent normal conjunctiva. ELISA also revealed that the average level of 8-OHdG in the pterygium tissues was 4.7-fold higher than that of the corresponding normal conjunctiva (P<0.001). CONCLUSIONS: The increased levels of 8-OHdG in the pterygium tissues indicate that oxidative stress could play a role in the development of pterygium. These findings provide new information to better understand the pathogenesis of pterygium and are useful in the prevention and treatment of this disease.

Genetic polymorphism of hOGG1 and risk of pterygium in Chinese.

PURPOSE: Ultraviolet irradiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. The highly mutagenic 8-hydroxy-2'-deoxyguanosine, a marker for the evaluation of photo-oxidative DNA damage, can be repaired by human 8-oxoguanine glycosylase I (hOGG1). A transition of C to G at nucleotide position 1245 in exon 7 of the hOGG1 gene is associated with the substitution of cysteine for serine at codon 326. In this study, we investigated the association of the hOGG1 Ser326Cys polymorphism with pterygium in a Chinese population. METHODS: In all, 70 patients and 86 controls were enrolled in this study. The Ser326Cys polymorphism was determined by the polymerase chain reaction-restriction fragment-length polymorphism analysis. The association between this genetic polymorphism and risk of pterygium was examined by chi(2)-test and logistic regression. RESULTS: The allelic frequencies for the Ser and Cys variants of hOGG1 gene were not significantly different between the two groups. However, when compared with Ser/Ser and Ser/Cys genotypes combined, we found that the homozygous Cys/Cys genotype was more prevalent in pterygium patients than controls (P=0.024) with the odds ratio being 2.2 (95% CI: 1.1-4.5). In the pterygium group, the mean age of patients with the Cys/Cys genotype was younger than those with the other two genotypes (P=0.025). CONCLUSIONS: Our findings suggest that the 1245C --> G transition in exon 7 of the hOGG1 gene, which results in Ser326Cys substitution of the enzyme, might play a role in the susceptibility of humans to pterygium.

A review of ocular emergencies in a Taiwanese medical center.

BACKGROUND: Ocular injury is one of the most common problems in the Emergency Department (ED), but a general survey of ocular injuries has rarely been reported in the literature. This article reviews cases of ocular injury collected in the ED of a medical center over a 12-month period. METHODS: A retrospective analysis was done on 1,314 consecutive patients who presented with eye complaints to the ED of the Veterans General Hospital-Taipei between November 1993 and October 1994. Common ocular diagnoses and their associated variables were assessed separately. RESULTS: Ocular injuries occurred in a male to female ratio of about 1.9:1 with a peak age in the third decade. Diagnoses were grouped as trauma (43.8%) and non-trauma (56.2%). Corneal abrasion was the most common trauma reported. The main circumstances of eye trauma were play (50.0%) in children (< 15 years), work (37.1%) in the age group of 16 to 59 years and domestic activity (45.8%) in patients over 60 years of age. Blunt objects and contusions (hits or falls) caused nearly 50% of all ocular injury cases. Most of the non-traumatic cases were due to acute conjunctivitis (19.1%), followed by contact lens (CL)-related disorders (11.4%). Three cases of CL-induced corneal ulcer resulted in permanent visual morbidity. There was a trend toward an increase in acute conjunctivitis in the summer, corneal ulcer in the spring and acute glaucoma in the winter. CONCLUSIONS: Young males were found to run a higher risk of ocular accidents, especially at work. Penetrating injuries with or without a retained intraocular foreign body were the leading cause of poor visual outcomes and often occurred in patients without protective eyeglasses. With the widespread use of CLs, many potentially serious complications were noted in the ED, which deserve attention.

Primary orbital hemangiopericytoma: a case report.

A case of primary orbital hemangiopericytoma is reported in a 31-year-old female presenting with progressive proptosis of the left eye and deteriorating diplopia over a period of 2 years. Orbital computed tomography revealed a superiorly located well-circumscribed extraconal mass. A 32x57x16 mm soft mass that appeared grossly encapsulated was removed intact via anterior orbitotomy. Histopathological examination disclosed it to be a hemangiopericytoma. The clinical importance is its potentially malignant behavior, with a high local recurrence rate in case of incomplete excision. Literature was reviewed.