Bacterial endotoxin and non-alcoholic fatty liver disease in the general population: a prospective cohort study.

BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth. AIMS: To test the hypothesis that endotoxemia is associated with non-alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia. METHODS: Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton-magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays. RESULTS: Two hundred and sixty-three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin-18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin-A levels than nondrinkers. CONCLUSIONS: Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies.

Contribution of SNRNP200 sequence variations to retinitis pigmentosa.

PURPOSE: Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients. METHODS: Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12-16, 22-32, and 38-45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses. RESULTS: Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study. CONCLUSIONS: Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP.

Quantitative assessment of optic nerve head morphology and retinal nerve fibre layer in non-arteritic anterior ischaemic optic neuropathy with optical coherence tomography and confocal scanning laser ophthalmoloscopy.

BACKGROUND/AIMS: To compare the optic disc parameters between patients with non-arteritic anterior ischaemic optic neuropathy (NAION) and normal controls, using optical coherence tomography (OCT) and Heidelberg Retinal Tomograph III (HRT), and to evaluate the structure-function relationship in NAION eyes. METHODS: Both eyes of 22 patients with typical unilateral NAION of > or =6 months' duration and 52 eyes from 52 randomly selected normal subjects underwent Humphrey visual field (HVF) examination and measurement of optic disc and retinal nerve fibre layer thickness (RNFLT). RESULTS: For the NAION-affected eyes, NAION fellow eyes and normal controls, the ocular magnification-corrected OCT disc areas were respectively 1.849 (SD 0.343) mm(2), 1.809 (0.285) mm(2) and 1.964 (0.386) mm(2); the cup areas were 0.246 (0.187) mm(2), 0.172 (0.180) mm(2) and 0.469 (0.332) mm(2). On HRT, the disc areas were 2.11 (0.38) mm(2), 2.06 (0.40) mm(2) and 2.16 (0.42) mm(2); and the cup areas were 0.28 (0.34) mm(2), 0.25 (0.18) mm(2) and 0.48 (0.32) mm(2). On both OCT and HRT, the cup areas and cup-disc area ratios (CDAR) of both eyes of NAION patients were significantly smaller than controls (p< or =0.01), but the disc areas were not (p> or =0.21). There was a significant correlation between HVF mean deviation and OCT RNFLT (r = 0.44, p = 0.04) but not with HRT RNFLT (p = 0.30) in NAION-affected eyes. CONCLUSION: NAION patients have smaller optic cups and CDARs in both eyes compared with controls. A larger sample size is necessary to demonstrate if disc size affects the risk of developing NAION. The NAION-affected eyes' OCT RNFLT correlated with HVF mean deviation but the HRT RNFLT did not.

Effects of the duration of initial oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada disease.

PURPOSE: To evaluate the effects of the duration of oral corticosteroid treatment on the recurrence of inflammation in Vogt-Koyanagi-Harada (VKH) disease. METHODS: Retrospective analysis of 35 VKH patients who received oral corticosteroid during the first attack of VKH with a minimum follow-up of 6 months. Patients were divided into two groups on the basis of the oral corticosteroid treatment duration of less than 6 months or 6 months or more. Kaplan-Meier survival and Cox-regression analyses were carried out to compare the recurrence rates of inflammation in the two groups. RESULTS: The mean age of onset was 42.5 years and the mean follow-up duration was 3.6 years. During the follow-up period, 10 (58.8%) of the 17 patients who received oral corticosteroid for less than 6 months compared with 2 (11.1%) of the 18 patients who had treatment for 6 months or more developed recurrence of inflammation (P=0.003). Cox-regression analysis showed that the duration of oral corticosteroid treatment for less than 6 months was the only significant risk factor for recurrence of VKH after adjustment for age, gender, and the initial dosage of oral corticosteroid treatment (adjusted odds ratio=8.8, P=0.008). Patients who received oral corticosteroid treatment for less than 6 months were also more likely to have one eye with visual acuity of 20/200 or worse (P=0.016). CONCLUSIONS: Early withdrawal of oral corticosteroid is associated with increased risk of recurrence of VKH and worse visual prognosis. Oral corticosteroid should be tapered off slowly and maintained for at least 6 months for the treatment of acute VKH.

Decreasing efficacy of repeated intravitreal triamcinolone injections in diabetic macular oedema.

BACKGROUND/AIM: Intravitreal triamcinolone (IVTA) results in transient improvements in diabetic macular oedema (DMO), necessitating repeated injections. The authors report a case series of 10 eyes of 10 patients with DMO, who received a repeat injection of 4 mg IVTA, at least 26 weeks after the first injection of the same dose. METHOD: Pre-injection and at 2, 4, 9, and 17 weeks post-injection, best corrected visual acuity (BCVA) and central foveal thickness (CFT) on optical coherence tomography, after the first and repeat injections, were compared using paired t test. Side effects were monitored. RESULTS: BCVA, CFT, intraocular pressure (IOP), and cataract scores were not significantly different before initial and repeat injections (given at 32.5 (SD 3.5) weeks after the first injection). Transient improvements of BCVA and CFT were achieved after both injections. However, after the repeat injection, the BCVA was significantly worse at all time points (p<0.05) and so were the best achieved CFT and the CFT at 4 weeks post-injection (p = 0.034 and 0.011 respectively), compared with the initial injection. Post-injection maximum IOPs and increase in cataract scores were not significantly different between the two injections. CONCLUSION: A repeat injection of 4 mg of IVTA may not be as effective as an initial injection for the treatment of DMO.

Phacoemulsification with intravitreal triamcinolone in patients with cataract and coexisting diabetic macular oedema: a 6-month prospective pilot study.

AIMS: To assess the safety and efficacy of phacoemulsification with intravitreal triamcinolone (ivTA) injection in diabetics with cataract and clinically significant macular oedema (CSMO). METHODS: A total of 19 eyes of 15 consecutive diabetic patients with cataract and CSMO were prospectively recruited. Patients underwent phacoemulsification and intraocular lens implantation with 4 mg ivTA injection at completion of surgery. Patients were followed up on day 1, then weekly for 1 month, and thereafter monthly until 6 months postoperatively. Best corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography, and adverse events were recorded. RESULTS: In total, 17 eyes completed 6 months of follow-up. In all, 58.8% showed improvement in BCVA of >or=2 lines, with statistically significant improvement in mean Snellen BCVA of 2.4 lines at 6 months. The peak BCVA was achieved at 4 months. The mean CMT decreased from a baseline of 449 microm to a minimum of 321+/-148 microm (28.5% reduction) achieved at 2 months, with statistically significant reduction at all postoperative time intervals until 6 months. Of 17 eyes, 4 (23.5%) developed transiently elevated intraocular pressure that normalised by 6 months in all but one patient. No injection- or surgery-related complications were encountered. CONCLUSIONS: Phacoemulsification with concurrent 4 mg ivTA injection appears to be a safe option for managing diabetics with cataract and CSMO. However, large-scaled randomised controlled trials are necessary for delineating the relative contributions of cataract removal and CMT reduction to visual improvement. Moreover, the transient effect on CMT may warrant further studies to determine optimal timing and dosage of further ivTA injections.

Ocular-hypertensive response and corneal endothelial changes after intravitreal triamcinolone injections in Chinese subjects: a 6-month follow-up study.

PURPOSE: To assess the intraocular pressure (IOP) and corneal endothelial changes, over a 6-month period, after a single injection of intravitreal triamcinolone (ivTA) in Chinese patients. METHODS: A total of 43 eyes of 43 consecutive Chinese patients with various macular diseases received a single bolus injection of 4 mg ivTA, of which, 14 eyes with significant cataracts underwent simultaneous phacoemulsification and primary intraocular lens implantation. IOP was measured preoperatively and weekly in the first month, and then monthly until 6 months postinjection. Specular microscopy was performed on 24 of the 29 eyes without simultaneous cataract surgery, preoperatively and at months 1, 3, and 6. RESULTS: All patients completed 6 months of follow-up. Nine out of 43 (20.9%) eyes had IOP >21 mmHg. Their mean maximum IOP was 29.2 mmHg (range 23.0-37.0), necessitating the use of 2.0 types of topical antiglaucomatous medications on average. The IOP elevation occurred at a mean of 5.2 weeks (range 1-17) postinjection. All IOPs returned to normal, without additional antiglaucomatous medications, by 6 months. There was no statistically significant difference (paired t-test, P<0.05) in the corneal endothelial cell count and other specular microscopy parameters up to 6 months after the injections. CONCLUSION: A single 4 mg bolus injection of ivTA appeared to have no harmful effects on the corneal endothelium. IvTA caused transient IOP elevations in 20.9% of Chinese patients, similar to that observed in Caucasians. As the IOP rise can occur as early as 1 week after the injection, early monitoring will help its early detection and prevent optic nerve damage.

Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level.

AIMS: To evaluate the changes in the choroidal vasculature in central serous chorioretinopathy (CSC) after photodynamic therapy (PDT) with verteporfin and to assess its potential role as a treatment option. METHODS: A prospective, non-comparative, interventional study was performed in eyes with persistent CSC or chronic CSC that had fluorescein leakage at the fovea. All eyes received one single session of PDT with verteporfin (6 mg/m2 body surface area) followed by application of 50 J/cm2 laser at 689 nm. The laser spot size was guided by findings in ICG-A. RESULTS: Six eyes from six patients with a mean follow up of 12.7 months were analysed. Narrowing of the original dilated choroidal vessels and decrease in extravascular leakage could be demonstrated in all (100%) PDT treated eyes. 3 months after PDT, the mean diameter of the dilated choroidal vessel reduced from 546 microm to 371 microm (p=0.028). Five (83%) patients had improvement in visual symptoms and best corrected visual acuity. Fluorescence leakage stopped at the 1 month follow up in five eyes (83%) and at 3 months in all six eyes (100%). One eye developed choroidal neovascularisation at 3 month follow up. There was no other serious ocular or systemic complication. CONCLUSIONS: PDT is successful in stopping the fluorescein leakage in all six patients without recurrence of CSC. The ICG-A findings of choroidal vascular remodelling and decreased choroidal permeability after PDT are encouraging. As the sample size is small and the mean follow up period is short, further trials of PDT with verteporfin for CSC are required to address the optimal parameters in ensuring longer term safety and efficacy outcome.