Role of cyclooxygenase-2 in H5N1 viral pathogenesis and the potential use of its inhibitors

1. Cyclooxygenase-2 (COX-2), along with TNF-α and other proinflammatory cytokines, was hyperinduced in H5N1- infected macrophages in vitro and in epithelial cells of autopsied lung tissues of infected patients. 2. The COX-2 mediated amplification of the proinflammatory response is rapid, and the effects elicited by the H5N1-triggered proinflammatory cascade are broader than those arising from direct viral infection. 3. Selective COX-2 inhibitors suppress the H5N1- hyperinduced cytokines in the proinflammatory cascade.published_or_final_versio

Prospective study on retinal nerve fibre layer changes after an acute episode of phacomorphic angle closure

To investigate the retinal nerve fibre layer (RNFL) changes after an acute attack of phacomorphic angle closure. This prospective study involved ten cases of phacomorphic angle closure that underwent cataract extraction and intraocular lens insertion after intraocular pressure lowering. Apart from visual acuity and intraocular pressure (IOP), RNFL thickness and vertical cup disc ratio (VCDR) were measured by optical coherence tomography (OCT) at 3-9 months post attack. Humphrey visual field assessment was performed at 9 months post attack. All cases had mean phacomorphic duration of  0.2. Patients with <5 days duration of phacomorphic angle closure are likely to have reasonable postoperative vision. An acute episode of phacomorphic angle closure can trigger an accelerated RNFL thinning despite normal IOP and open angles, most noticeable in the superior and inferior quadrants, occurring between 3 and 9 months post attack. Glaucomatous optic neuropathy in the attack eye was evident by OCT but not by visual field assessment at the same time interval. © 2012 The Author(s).published_or_final_versio

Argon laser peripheral iridoplasty versus systemic intraocular pressure-lowering medications as immediate management for acute phacomorphic angle closure.

Background: The purpose of this study was to compare the efficacy and safety of argon laser peripheral iridoplasty (ALPI) and systemic intraocular pressure (IOP)-lowering medications in the immediate management of acute phacomorphic angle closure. Methods: Consecutive cases of acute phacomorphic angle closure were randomized to receive ALPI and an intravenous or oral carbonic anhydrase inhibitor as initial treatment. Intravenous mannitol was administered for presenting IOP > 60 mmHg or IOP > 40 mmHg 2 hours posttreatment in both arms. Results: Of 10 consecutive cases, six received medical therapy and four received ALPI. Fifty percent in the medical group and none in the ALPI group required intravenous mannitol. The ALPI group took less time to achieve IOP < 25 mmHg (18.8 ± 7.5 minutes versus 115.0 ± 97.0 minutes, P = 0.001, F test); had a greater IOP reduction within 30 minutes (69.8% ± 7.7% versus 40.9 ± 23.9%, P = 0.03, t-test); and had a consistently smaller post-attack cup to disc ratio (0.50 ± 0.02 versus 0.60 ± 0.20, P = 0.002, F test). Conclusion: ALPI offers greater safety, consistency, and efficacy than systemic IOP-lowering medications as initial treatment for phacomorphic angle closure. © 2013 Lee et al, publisher and licensee Dove Medical Press Ltd.published_or_final_versio

Two-Year Clinical Results After Selective Laser Trabeculoplasty for Normal Tension Glaucoma

Open Access JournalThis article aims to investigate the clinical results at 2 years after selective laser trabeculoplasty (SLT) for normal tension glaucoma (NTG). This prospective cohort study recruited NTG patients taking antiglaucoma medication. Subjects were excluded if they had previous glaucoma surgery/laser or corneal pathologies. All subjects underwent a 1-month washout. A single session of SLT was performed to 360° of the trabecular meshwork. Medication was resumed at 1 month to achieve a targeted 30% intraocular pressure (IOP) reduction from the post-washout/pre-SLT IOP. IOP was measured every 3 months and medication use was recorded at 3, 6, 12, and 24 months. Subjects with a secondary SLT or cataract extraction were excluded from IOP and medication analyses. At 24 months, 34 of the initial 45 right eyes were eligible for analyses. There were significant IOP reductions at all time intervals (except at 1 week) following SLT when compared to the prestudy (without medication) or pre-SLT (post-washout) IOP (P 20% from pre-SLT, without medication) was achieved in 11.1% (5/45). Reductions in IOP and medication use were evident at 2 years following SLT for the treatment of NTG whereas 11% remained medication free. Trial Registrations: The Clinical Trials Register of the University of Hong Kong HKCTR1847. The European Clinical Trials Database 2014-003305-15 (August 11, 2014).published_or_final_versio

Argon laser peripheral iridoplasty (ALPI) versus systemic intraocular pressure lowering medications as the immediate management for phacomorphic angle closure

Poster Session: Glaucoma PhenotypesPurpose: To compare the efficacy and safety of argon laser peripheral iridoplasty (ALPI) to systemic intraocular pressure (IOP) lowering medications in the immediate management of phacomorphic angle closure. Patients and methods: This was a prospective randomized controlled study conducted at a district hospital in Hong Kong, China. Consecutive cases of phacomorphic angle closure were recruited from December 2009 to December 2010. Patients received intravenous (IV) and oral carbonic anhydrase inhibitor or ALPI as the initial treatment. IV mannitol was administered in both groups for presenting IOP > 60 mmHg or IOP > 40 mmHg 2 hours post treatment. The following perimeters were compared between the 2 arms: Snellen best correct visual acuity (BCVA); duration of symptoms; presenting IOP; IOP at 15 minutes, 30minutes and hourly after treatment until IOP < 25 mmHg; post-op angle, retinal nerve fibre layer (RNFL), endothelial count, BCVA and IOP. Results: Ten consecutive cases were included in the study. Six cases received medication therapy and 4 received ALPI. The mean age was 79.7 ± 7.2 in the medical therapy group and 78.3 ± 11.0 in the ALPI group. The presenting IOP was 50.7 ± 8.4 mmHg and 50.25 ± 6.9 mmHg in the medical therapy and ALPI group respectively. The duration of phacomorphic glaucoma in the medical group was 2.8 ± 3.5 days and 0.9 ± 0.25 days in the ALPI group. In the medical therapy group, 50% (3/6) required IV mannitol and none in the ALPI group. The time taken to reduce the presenting IOP to < 25 mmHg was 115.0 ± 97.0 minutes in the medical therapy group and 18.8 ± 7.5 minutes in the ALPI group. Within the first 30minutes, the drop in IOP was 20.8 ± 13.5mmHg in the medical group and 34.8 ± 3.2mmHg in the ALPI group, representing a 41.0% and 69.3% drop in IOP respectively. The degree of peripheral anterior synechiae (PAS) formation at 3 months was 45 ± 45.3° and 22.5 ± 5° in the medical and ALPI group respectively. The RNFL, angle, endothelial count, post-op VA and IOP were comparable in both groups. Conclusion: ALPI is an effective and safe IOP lowering modality in acute phacomorphic angle closure, offering a more rapid reduction of IOP, avoiding the use of systemic carbonic anhydrase inhibitor and hyperosmotic agents, and with seemingly less PAS formation and comparable post-op results as compared to medical therapy. ALPI should replace medical therapy as first line treatment in phacomorphic angle closure especially in elderly patients cannot tolerable the side effects of systemic IOP-lowering medication.published_or_final_versio

The Association Between Clinical Parameters And Glaucoma-specific Quality Of Life In Chinese Primary Open-angle Glaucoma Patients

Objective: To investigate the association between clinical measurements and glaucoma-specific quality of life in Chinese glaucoma patients. Design: Cross-sectional study. Setting: An academic hospital in Hong Kong. Patients: A Chinese translation of the Glaucoma Quality of Life–15 questionnaire was completed by 51 consecutive patients with bilateral primary open-angle glaucoma. The binocular means of several clinical measurements were correlated with Glaucoma Quality of Life–15 findings using Pearson’s correlation coefficient and linear regression. The measurements were the visual field index and pattern standard deviation from the Humphrey Field Analyzer, Snellen best-corrected visual acuity, presenting intra-ocular pressure, current intra-ocular pressure, average retinal nerve fibre layer thickness via optical coherence tomography, and the number of topical anti-glaucoma medications being used. Results: In these patients, there was a significant correlation and linear relationship between a poorer Glaucoma Quality of Life–15 score and a lower visual field index (r=0.3, r2=0.1, P=0.01) and visual acuity (r=0.3, r2=0.1, P=0.03). A thinner retinal nerve fibre layer also correlated with a poorer Glaucoma Quality of Life–15 score, but did not attain statistical significance (r=0.3, P=0.07). There were no statistically significant correlations for the other clinical parameters with the Glaucoma Quality of Life–15 scores (all P values being >0.7). The three most problematic activities affecting quality of life were “adjusting to bright lights”, “going from a light to a dark room or vice versa”, and “seeing at night”. Conclusion: For Chinese primary open-angle glaucoma patients, binocular visual field index and visual acuity correlated linearly with glaucoma- specific quality of life, and activities involving dark adaptation were the most problematic.published_or_final_versio

Detection of glaucoma in a cohort of chinese subjects with systemic hypertension

Purpose. To determine the presence and type of glaucoma in a cohort of adult Chinese subjects with systemic hypertension. Methods. This prospective cohort study included 200 hypertensive Chinese adults aged >40 years old who underwent screening via frequency doubling technology (FDT) perimetry and intraocular pressure (IOP) measurement by noncontact tonometry (NCT) in a general outpatient clinic. Those with IOP > 21 mmHg and/or visual field (VF) defects on FDT were referred for complete ophthalmological examination. The diagnosis of glaucoma was based on an abnormal VF on Humphrey Field Analyzer (HFA) by Hodapp-Parrish-Anderson's criteria and an increased vertical cup-disc ratio (VCDR). Results. The mean age of the subjects was 64.66 ± 9.47 years, and the male:female ratio was 92: 108. All patients were hypertensive with a mean blood pressure (BP) of 131.1 ± 15.1 / 76.6 ± 11.1 mmHg whilst on systemic antihypertensive medication. Of the 111 patients that had an abnormal initial screening, 14 (7.9%) were confirmed to have glaucoma with the highest prevalence of normal tension glaucoma (NTG) (6.2%), followed by primary angle closure glaucoma (PACG) (1.1%) and primary open angle glaucoma (POAG) (0.5%). The positive predictive value of FDT perimetry was 71%. Conclusion. Nearly 8% of the adults with systemic hypertension had glaucoma, and NTG was the most prevalent type. © 2013 Rita A. Gangwani et al.published_or_final_versio

Retinal Nerve Fiber Layer Thickness in Myopic, Emmetropic, and Hyperopic Children

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Angiopoietin-1 and keratinocyte growth factor restore the impaired alveolar fluid clearance induced by influenza H5N1 virus infection

Poster Session: Novel TherapeuticsBackground: Acute respiratory distress syndrome (ARDS) caused by high pathogenic avian influenza (HPAI) H5N1 virus infection has resulted in severe illness and high mortality rates among patients. Patients with ARDS are often characterized by impaired alveolar fluid clearance and alveolar edema. An understanding of the mechanism responsible for human alveolar edema will lead to the development of novel therapeutic treatments for ARDS patients. We hypothesized that the paracrine soluble factors angiopoietin-1 (Ang-1) and keratinocyte growth factor (KGF) can resolve alveolar fluid clearance by up-regulating the expression of major sodium and chloride transporters impaired by HPAI H5N1 virus infection. Materials and Methods: Human alveolar epithelial cells grown on transwell inserts were infected with HPAI H5N1 (A/HK/483/97) and low pathogenic avian influenza (LPAI) H1N1 (A/HK/54/98) viruses at MOI 0.1 or incubated with conditioned culture medium containing Ang-1 and/or KGF. At 24 and 48 h post-infection, the rate of alveolar fluid transport and protein permeability across the alveolar epithelium was measured. Protein expression of sodium and chloride transporters (Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit) was measured by qPCR, ELISA, and Western blot. Results: HPAI H5N1 (A/HK/483/97) virus infection significantly reduced net alveolar fluid transport and protein permeability when compared with H1N1 (A/HK/54/98) virus infection at 24 h post-infection and further reduced it at 48 h post-infection. This reduction in alveolar fluid clearance was associated with a substantial reduction in protein expression of Na-K-ATPase, CFTR, and epithelial sodium channel alpha subunit. The influenza virus–infected cells treated with Ang-1 and KGF restored the impaired alveolar edema fluid clearance and protein permeability after HPAI H5N1 virus infection. Furthermore, the paracrine soluble factors Ang-1 and KGF up-regulated the protein expression of the major sodium and chloride transporters resulting from the HPAI influenza virus infection. Conclusions: The paracrine soluble factors Ang-1 and KGF play an important role in maintaining human alveolar fluid clearance by up-regulating the sodium and chloride transporting systems in human alveolar epithelium. This study enriches the understanding of the development of ARDS in human H5N1 disease and may aid in the development of possible therapeutic applications.published_or_final_versio

Using electrical stimulation to enhance the efficacy of cell transplantation therapies for neurodegenerative retinal diseases: Concepts, challenges, and future perspectives

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