Shwu-Jiuan Sheu

Ocular manifestations of tuberculosis

OBJECTIVE To present the clinical and histopathologic findings in five cases of tuberculosis (TB) with various ocular manifestations. DESIGN Observational case series. METHODS Retrospective review of clinical findings, course, and treatment of five patients. Diagnostic techniques, including biomicroscopic, histopathologic, and molecular biologic test results, are presented. MAIN OUTCOME MEASURES Visual acuity, slit-lamp biomicroscopy, indirect ophthalmoscopy, and fluorescein angiography results. RESULTS The ocular manifestations of TB in our patients included panophthalmitis, endophthalmitis, posterior uveitis with choroidal tubercles, keratitis, and a lid mass. Mycobacterium tuberculosis was identified in four cases in ocular specimens using acid-fast bacilli microscopy and in three cases by culture. Rapid diagnosis using polymerase chain reaction was obtained in one case. Extraocular foci of TB were identified in three cases with an intraocular infection at presentation. No patients had the human immunodeficiency virus (HIV) and none were immunocompromised. Two eyes could not be saved using antituberculous treatment because of delayed diagnosis and treatment. CONCLUSIONS In this age of the HIV pandemic, TB is becoming more common. Because it is curable, heightened awareness and better understanding of the diseases ocular manifestations should be of concern to all ophthalmologists.

What factors are associated with myopia in young adults? A survey study in Taiwan Military Conscripts.

PURPOSE We investigated the independent impact of potential risk factors on myopia in young adults. METHODS A survey study was conducted with male military conscripts aged 18 to 24 years between February 2010 and March 2011 in Taiwan. The participants were examined using non-cycloplegic autorefraction and biometry. The participants provided data about potential risk factors, including age, parental myopia, education, near work, outdoor activity, and urbanization. Myopia was defined as the mean spherical equivalent of the right eye of ≤ 0.5 diopters (D). RESULTS Among 5145 eligible participants, 5048 (98.11%) had refraction and questionnaire data available; 2316 (45.88%) of these received axial length examination. The prevalence of myopia was 86.1% with a mean refractive error of -3.66 D (SD = 2.73) and an axial length of 25.40 mm (SD = 1.38). Older age, having myopic parents, higher education level, more time spent reading, nearer reading distance, less outdoor activity, and higher urbanization level were associated with myopia and longer axial length. More computer use was related to longer axial length. All risk factors associated with myopia also were predictors of high myopia (≤ -6.0 D), with the exception of outdoor activity. Finally, an interaction analysis showed shorter axial length was associated with more time spent outdoors only at high urbanization level. CONCLUSIONS Older age, parental myopia, higher education level, more near work, less outdoor activity, and higher urbanization level were independent predictors of myopia. These data provided evidence to the multifactorial nature of myopia in young men in Taiwan.

Resveratrol Protects Human Retinal Pigment Epithelial Cells from Acrolein-Induced Damage

PURPOSE Although the exact pathogenesis of age-related macular degeneration (AMD) is not clear, most studies indicate a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The purpose of this study was to examine the potential protective effects of lutein, zeaxanthin, meclofenamic acid, and resveratrol on the acrolein-induced oxidative stress in human RPE cells. METHODS Cultured human RPE R-50 cells were treated with acrolein at different concentrations and treatment times. The protective effects of lutein (100 microM), zeaxanthin (100 microM), meclofenamic acid (30 microM), and resveratrol (10 microM) were investigated by pretreatment with the above agents before toxicant exposure in acute toxicity models and cotreatment with the toxicant in chronic toxicity models. The synergistic effects of acrolein and hydrogen peroxide exposure were also studied. Fluorescent latex beads were used to assess the phagocytic function of the cells. RESULTS Acrolein inhibited the phagocytic function of human RPE R-50 cells, and the inhibitory effects were time dependent. Pretreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol alleviated the inhibition of phagocytosis in the acute acrolein and combined acrolein/hydrogen peroxide toxicity models. Synergistic effects were seen between zeaxanthin and resveratrol or meclofenamic acid. Cotreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol showed a protective effect against the damage caused by 7-day acrolein exposure followed by hydrogen peroxide treatment. CONCLUSIONS Our results indicated an inhibitory effect of compounds found in cigarette smoke on human RPE phagocytosis, and lutein, zeaxanthin, meclofenamic acid, and resveratrol each offered protection against this inhibition. Therefore, red wine polyphenol, resveratrol, might ameliorate acrolein-induced or age-related RPE degeneration, such as AMD.

Resveratrol Stimulates Mitochondrial Bioenergetics to Protect Retinal Pigment Epithelial Cells From Oxidative Damage

PURPOSE Resveratrol (RSV) alleviates oxidative damage in human adult retinal pigment epithelial (ARPE) cells. Mitochondrial bioenergetics is associated with oxidative stress. The purpose of this study was to examine the role of mitochondrial bioenergetics in the cytoprotective effect of RSV. Its role in protection against the adverse effects of cigarette smoke (CS) in experimental choroidal neovascularization (CNV) was also examined. METHODS Cultured ARPE-19 cells were treated with acrolein alone or acrolein with added RSV. Temporal changes in cell viability, expression of the antioxidant protein, and mitochondrial bioenergetics were evaluated. In an animal study, CNV lesions were created in Brown Norway rats by laser-induced photocoagulation. Effects of CS alone or with additional RSV treatment on CNV lesions were quantified by fundus fluorescein angiography. RESULTS In ARPE-19 cells, RSV rescued acrolein-induced cell death, alongside reversal of acrolein-induced superoxide dismutase expression. Resveratrol increased the mitochondrial bioenergetics, including basal respiratory rate, adenosine triphosphate synthesis via oxidative phosphorylation, and maximal mitochondrial capacity. In animal experiments, CS induced a significant increase in CNV following laser injury, and this increase in CNV was appreciably prevented following peripheral infusion of RSV. CONCLUSIONS Our results indicate that RSV, a major polyphenol found in red wine, exerts protection against acrolein-induced cytotoxicity in human ARPE-19 cells via increases in the mitochondrial bioenergetics. In addition, the antioxidant effect of RSV may contribute to protection against laser-induced CNV in animals exposed to CS. Therefore, RSV might be beneficial for treatment of acrolein-induced or CS-evoked RPE degeneration.

Ocular Uveitis as the Initial Presentation of Syphilis

Background: To document the characteristics of syphilitic patients who present with ocular uveitis clinically and are diagnosed by an ophthalmologist first. Methods: Retrospective chart review of uveitis patients in the department of ophthalmology between 1992 and 2004 was done. We included only those patients with positive serologic tests, active ocular uveitis, and record of detailed examination. Results: There were 8 syphilitic patients (14 eyes) who presented with ocular syphilis clinically and who were diagnosed by an ophthalmologist first. The ocular diagnosis included panuveitis (11 eyes, 78.6%), anterior uveitis (2 eyes, 14.3%), and posterior uveitis (1 eye, 7.1%). Two patients (25%) had unilateral eye involvement, and 6 patients (75%) had involvement in bilateral eyes. One patient (2 eyes) with panuveitis also had bilateral exudative retinal detachment and chronic angle closure glaucoma. All 8 patients were negative for human immunodeficiency virus. Dark field examination of aqueous humor in 2 cases revealed Treponema pallidum, which was confirmed by immunofluorescent test. Treatment included systemic penicillin in 7 patients and oral tetracycline in 1 patient (due to penicillin allergy). Visual function and uveitis improved after treatment in all patients. Conclusion: Syphilis can be presented initially as ocular uveitis without obvious systemic manifestation. Ophthalmologists play an important role in the early diagnosis and treatment of syphilis. If treated early enough, the response is good, even if the patient is allergic to penicillin. Awareness of the multiple manifestations of ocular syphilis is the key to early detection of the disease.

Optic Neuritis: Clinical Analysis of 27 Cases

We retrospectively reviewed 27 cases diagnosed as idiopathic optic neuritis between 1992 and 2001 at Kaohsiung Veterans General Hospital to assess the clinical features, visual prognosis, neuroimaging, laboratory studies, and development of multiple sclerosis in Chinese patients with optic neuritis. Patient age ranged from 13 to 54 years (mean, 35.8 ± 11.3 years). Five cases presented as bilateral optic neuritis and 22 as unilateral. Visual function improved gradually from 2 weeks after treatment. Twelve (44.4%) cases showed disc swelling and ocular pain was also noted in 44.4% of patients. All cases that underwent visual field and visual evoked potential tests showed abnormality in lesion eyes. Of the 23 cases that underwent neuroimaging studies, including computerized tomography (17 patients) and magnetic resonance imaging (6 patients), 10 revealed optic nerve thickening. Four cases (14.8%) developed multiple sclerosis during follow‐up (mean, 4.3 years). The incidence of disc swelling was higher than that reported by the Optic Neuritis Treatment Trial, but the incidence of initial ocular pain, the presence of periventricular plaques, and the development of multiple sclerosis were lower in our study. The unilateral group had significantly better visual outcome than the bilateral group.

Resveratrol and Large-Conductance Calcium-Activated Potassium Channels in the Protection of Human Retinal Pigment Epithelial Cells

This study was undertaken to examine the possible association of large-conductance calcium-activated potassium channels (BK(Ca) channels) and human retinal pigment epithelial (RPE) R-50 cell phagocytosis. The potential antioxidative effect of resveratrol in human RPE cells also was investigated. Cultured human RPE R-50cells were treated with hydrogen peroxide ( H(2)O(2), 10 microM, 20 min), meclofenamic acid (30 microM, 20 min), paxilline (100 nM, 20 min), or resveratrol (10 microM, 20 min), respectively. Meclofenamic acid (30 microM, 20 min) or resveratrol (10 microM, 20 min) was given after exposure to H(2)O(2) . Pretreatment with meclofenamic acid, resveratrol, or paxilline before H(2)O(2) exposure also was performed. Fluorescent latex beads then were fed for 4 h, and phagocytic function was assessed by flow cytometry. H(2)O(2) inhibited the phagocytic function of human RPE R-50 cells. The BK(Ca) channel inhibitor, paxilline, inhibited RPE phagocytosis, as did hyperoxide stress. The BK(Ca) channel opener, meclofenamic acid, prevented the damage caused by H(2)O(2) . Pretreatment with resveratrol also provided protection against damage caused by H(2)O(2) . However, further treatment with resveratrol or meclofenamic acid was not found to offer protection from H(2)O(2) exposure. In conclusion, the dietary antioxidant, resveratrol, significantly reduced oxidative damage on phagocytic function in human RPE R-50 cells. One of the underlying mechanisms might be linked to the activity of BK(Ca) channels in RPE cells.

Risk Factors For and Progression of Myopia in Young Taiwanese Men

Abstract Purpose: To investigate the association between potential risk factors for myopia and its progression in young adult Taiwanese men. Methods: A survey of male military conscripts (aged 18–24 years) was conducted from February 2010 to March 2011 in Taiwan. Participants underwent comprehensive eye examinations, including measurements of axial length and corneal radius by optical biometry and non-cycloplegic autorefraction. Participants also provided self-reported progression of myopia and information regarding potential risk factors, including age, parental myopia, educational level, close work, outdoor activities, and urbanization. Results: Of 5145 eligible participants, 5048 (98.11%) provided refraction and questionnaire data; 2316 (45.88%) of the 5048 also had biometric measurements. The prevalence of myopia was 86.1% in this group, with a mean refractive error of −3.66 diopters (D). Of the 5048 participants, 1376 (27.3%) had experienced progression of their myopia during the past year. There were trends for a higher prevalence of myopia among older participants (p = 0.014), those with a history of parental myopia (p < 0.001), higher levels of education (p = 0.001), increased time spent reading (p < 0.001), less time outdoors (p = 0.003), and higher levels of urbanization (p = 0.010). However, only parental myopia, close work, and higher urbanization levels were significantly associated with self-reported progression of myopia. Conclusion: Older age, parental myopia, higher educational level, close work, fewer outdoor activities, and higher urbanization level were associated with the prevalence of myopia in Taiwanese men.

MACULAR HOLE IN BEHCET'S DISEASE

Behcets disease is an inflammatory disorder of unknown cause, characterized by recurrent oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Ocular involvement occurs in 60‐80% of patients with Behcets disease and presents as panuveitis in most cases. Posterior segment involvement may lead to irreversible alterations and significant vision loss. The development of a partial or full‐thickness macular hole, though rarely reported, may cause serious vision loss. In this report, we present two cases of macular hole in the worse eye of bilateral cases of Behcets disease, and discuss the possible mechanisms and management in such cases.

Gene Delivery by Subconjunctival Injection of Adenovirus in Rats: A Study of Local Distribution, Transgene Duration and Safety

Subconjunctival injection is a minimally invasive route for gene delivery to ocular tissues, but has traditionally been limited to use in the cornea. The accurate ocular distribution of virus has not, however, been previously investigated. Adenovirus is an attractive gene vector as it can deliver large genes and allow for short-term gene expression, but how safe it is when delivered via subconjunctival injection remains to be established. We have characterized the bio-distribution and safety of subconjunctivally administered adenovirus in Brown Norway rats. The bio-distribution and transgene duration of adenovirus carrying luciferase gene (Ad-Luci) at various time intervals were evaluated via bioluminescence imaging after subconjunctival injection. Adenovirus carrying a reporter gene, β-galactosidase (Ad-LacZ) or hrGFP (Ad-hrGFP) was administered subconjunctivally and the viral distribution in various ocular tissues was assessed by histological analysis and quantitative PCR (qPCR). Hepatic damage was assessed by biochemical and immunohistological analysis with TUNEL stain. Systemic immunogenicity was assessed by measuring serum level of TNF-α via ELISA, 2 hours and 14 days after administration of adenovirus. Retinal function was examined by electroretinography. Subconjunctival injection of Ad-Luci induced luciferase expression in the injected eyes within 24 hours, for at least 64 days. Histological analysis showed adenovirus distributed across anterior and posterior ocular tissues. qPCR demonstrated different amounts of adenovirus in different ocular tissues, with the highest amounts closest to the injection site Unlike the intravenous route, subconjunctivally delivered adenovirus did not elicit any detectable hepatic injury or systemic immunogenicity. Retinal function was unaffected by adenovirus irrespective of administration route. In conclusion, an adenoviral vector administered subconjunctivally can infiltrate into different ocular tissues and lead to short-term ocular transgene expression, without causing hepatic injury and immune activation. Therefore, subconjunctivally administered adenovirus may be a promising gene delivery approach for managing anterior and posterior segment eye diseases requiring short-term therapy.