Reduced choroidal peripapillary capillaries in thyroid-associated ophthalmopathy with early stage of dysthyroid optic neuropathy.

AIM: To investigate whether the subtle change of choroidal/retinal vessel densities and volumes in thyroid-associated ophthalmopathy (TAO) could be an early sign to detect dysthyroid optic neuropathy (DON). METHODS: This was a retrospective cross-sectional study, and a total of 98 eyes from 50 subjects were enrolled under certain criteria. Thirty-four eyes of normal controls and 64 eyes of TAO, including 39 eyes of DON and 25 eyes of TAO without DON, underwent optical coherence tomography angiography (OCTA) scanning. All the tested parameters of OCTA scanning including choroid radial peripapillary capillaries (RPC), retinal nerve fiber layer (RNFL), and macular ganglion cell complex (GCC) were compared among groups, and the correlation between OCTA parameters and visual function parameters was also investigated. RESULTS: Whole choroidal RPC was significantly reduced in DON (48.24%±0.4978%) compared to normal (50.33%±0.3173%) and TAO without DON (49.16%±0.5463%; P=0.0041). The reduction of whole choroidal RPC was also correlated with visual field (VF) defect in DON (r=0.5422, n=39). Although vision acuity and VF were improved in all the patients with DON after being treated with medical and surgical decompression, the reduction of RPC density were not reversed. CONCLUSION: There is a notable reduction in choroidal RPC in DON, which is correlated with VF defect. The reduction of RPC density could not be reversed immediately by medical and surgical decompression even when vision and VF were improved. These findings suggest that choroidal RPC could be a useful parameter to diagnose and monitor early stage of DON.

Changes in the structure of intestinal mucosal flora in colorectal cancer patients / 南方医科大学学报

OBJECTIVE@#To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC).@*METHODS@#We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit.@*RESULTS@#The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001).@*CONCLUSION@#The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.

The Potential Role of Osteopontin in the Pathogenesis of Graves' Ophthalmopathy.

Purpose: The aim of this study is to evaluate the expression of osteopontin (OPN) and its relationship with relative cytokines in patients with Graves' ophthalmopathy (GO), and to observe the effect of OPN on orbital fibroblasts (OFs) proliferation, migration, and the expression of relative cytokines, as well as the signaling pathways involved in its effect. Methods: The orbital adipose connective tissue was obtained from 24 patients with GO (12 cases of active GO, and 12 cases of inactive GO) and 12 healthy controls. OFs were isolated from orbital tissues obtained from patients with active GO who were undergoing orbital decompression surgery. Quantitative PCR and Western blot were performed to detect RNA and protein expression. The proliferation and cell migration rates of OFs were measured by methylthiazol tetrazolium (MTT) and the cell scratch test. Signaling pathway inhibitors, such as OPN monoclonal antibody 1A12, ERK1/2 inhibitor PD98059, and PI3K inhibitor LY294002, were applied to determine the involved pathways. Results: The mRNA and protein levels of OPN were increased in orbital adipose connective tissue from patients with active GO than those from patients with inactive GO (2.83-fold increase, P < 0.001; 1.91-fold increase, P < 0.05). The OPN mRNA level was positively correlated with CD40 ligand (CD40L) and hyaluronan synthases 2 (HAS2) mRNA in patients with GO. OPN promoted proliferation and migration rate of OFs and induced vascular endothelial growth factor (VEGF) and collagen I mRNA expression, and the effects were inhibited by 1A12 or LY294002. Conclusions: OPN in orbital adipose connective tissues were significantly increase in active GO, and there were significant correlations of OPN with CD40L and HAS2 mRNA levels in patients with GO. OPN promoted proliferation and migration of OFs and induced VEGF and collagen I mRNA expression in OFs through PI3K/Akt signaling pathway. This suggested a role for OPN in the pathogenesis of GO through the activation of OFs.

Intravenous glucocorticoids therapy in the treatment of Graves' ophthalmopathy: a systematic review and Meta-analysis.

AIM: To evaluate the benefit and harms of high-dose intravenous glucocorticoids (IVGC) as first-line treatment for Graves' ophthalmopathy (GO). METHODS: A systematic review and Meta-analysis of randomized clinical trials (RCTs) comparing IVGC for the treatment of GO, with placebo or other treatments, were conducted. Electronic databases were searched, and standard methodological guidance of Cochrane Handbook for Systematic Reviews of Interventions was used. The primary outcome was overall response, and secondary outcomes included the improvement and change in clinical activity score (CAS), and adverse events. RESULTS: Ten RCTs were included in the Meta-analysis. Low quality evidence (one trial) showed that participants receiving IVGC achieved significantly higher response compared to participants receiving placebo [risk ratio (RR) 7.50, 95% confidence interval (CI) 1.14 to 49.26]. Moderate quality evidence (four trials) support appreciable benefit of IVGC in response compared with oral glucocorticoids (OGC), with of RR being 1.51 (95%CI 1.25 to 1.83). There was low quality evidence (one trial) compatible with appreciable benefit for IVGC plus orbital radiotherapy in response (RR 1.38, 95%CI 1.07 to 1.79), compared with OGC plus orbital radiotherapy. One IVGC versus rituximab trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using rituximab (RR 0.70, 95%CI 0.50 to 0.98). One IVGC versus mycophenolate mofetil (MMF) trial provided moderate quality evidence suggesting that participants using IVGC achieved significantly lower response compared to participants using MMF (RR 0.74, 95%CI 0.63 to 0.88). Very low quality evidence (one trial) showed that participants with dysthyroid optic neuropathy (DON) receiving IVGC were more likely to achieve response compared to participants receiving orbital decompression (RR 3.33, 95%CI 0.51 to 21.89). CONCLUSION: The current evidence is moderate quality, which is sufficient to support IVGC to be as the first-line treatment for moderate-to-severe GO, and the use of rituximab or MMF to be the second-line treatment instead of IVGC. However, the evidence is very low quality, which is insufficient to support the use of IVGC or orbital decompression as the first-line treatment of DON.

A Systematic Review and Meta-Analysis of Clinical Outcomes of Intravitreal Anti-VEGF Agent Treatment Immediately after Cataract Surgery for Patients with Diabetic Retinopathy.

AIMS: To examine possible benefits of intravitreal anti-vascular endothelial growth factor (VEGF) agent treatment immediately after cataract surgery for patients with diabetic retinopathy (DR). METHODS: A comprehensive literature search was performed using the Cochrane collaboration methodology to identify randomized controlled trials (RCTs) and comparative studies of cataract surgery with or without anti-VEGF agent treatment for any diabetic retinopathy. Meta-analyses were performed for clinical outcome parameters including changes in macular thickness (MT), best-corrected visual acuity (BCVA), incidence of diabetic retinopathy and maculopathy progression, laser treatment rate, and other complications. RESULTS: Nine RCTs and 3 nonrandomized comparative studies were identified and used for comparing cataract surgery with intravitreal bevacizumab (IVB) or intravitreal ranibizumab (IVR) treatment (338 eyes, intervention group) to cataract surgery alone (329 eyes, control group). Analysis of all data showed that the mean BCVA at 1 week postoperatively had no statistically significant difference in the two groups, but at 1, 3, and 6 months postoperatively, the mean BCVA was statistically significantly better in the anti-VEGF treatment group than that in cataract surgery alone group. Analysis of all data showed that the mean MT was statistically significantly less in the anti-VEGF treatment group at 1 week and 1, 3, and 6 months postoperatively (P=0.05, P=0.006, P=0.0001, and P=0.0001, respectively); but postoperative clinical outcomes were differentiated from the type of anti-VEGF agents, IVB or IVR, and the existing macular edema preoperatively. Intravitreal anti-VEGF agent treatment statistically significantly reduced the incidence of diabetic retinopathy progression and maculopathy progression compared to the control group (P=0.0003, P < 0.00001, respectively). CONCLUSION: IVB or IVR treatment immediately after cataract surgery may represent a safe and effective strategy to prevent postoperative macular thickening or reduce macular edema and result in greater mean improvements in visual acuity for diabetic patients.

Altered Corneal Nerves in Chinese Thyroid-Associated Ophthalmopathy Patients Observed by In Vivo Confocal Microscopy.

BACKGROUND Thyroid-associated ophthalmopathy (TAO) is a common endocrine autoimmune disease. The present study explored corneal nerve changes in TAO patients. MATERIAL AND METHODS Thirty-eight Chinese TAO patients and 20 healthy individuals were included in the study. Central corneal subbasal nerve density and morphology were evaluated with in vivo laser scanning confocal microscopy and quantified using automated CCmetrics software. RESULTS The values of the central corneal subbasal nerve plexus parameters of both active and inactive TAO patients were significantly decreased compared with those of controls, including corneal nerve fiber density (CNFD) (P<0.001 for both), corneal nerve branch density (CNBD) (P<0.001 for both), corneal nerve fiber length (CNFL) (P<0.001 for both), corneal nerve fiber total branch density (CTBD) (P<0.001 for both), corneal nerve fiber area (CNFA) (P<0.001 for both), corneal nerve fiber width (CNFW) (P=0.046, P=0.027, respectively), and corneal nerve fiber fractal dimension (ACNFrD) (P<0.001 for both). In addition, CNFD and ACNFrD values were significantly lower in the active TAO patients compared with those in the inactive TAO patients (P=0.020, P=0.002, respectively). There were significant correlations between CNFD, CNBD, CNFL, CTBD, CNFA, and ACNFrD and the ocular surface parameters and activity assessment items. CONCLUSIONS Abnormal corneal subbasal nerves were observed in both active and inactive Chinese TAO patients, suggesting that nerve degeneration is associated with the disease. However, the exact underlying mechanisms remain to be elucidated.

Observation of Corneal Langerhans Cells by In Vivo Confocal Microscopy in Thyroid-Associated Ophthalmopathy.

PURPOSE: To examine the density and morphology of Langerhans cells (LCs) in the cornea of patients with thyroid-associated ophthalmopathy (TAO). METHODS: Forty patients with TAO and 20 healthy volunteers were studied. All subjects underwent a thorough ophthalmic examination of both eyes. The ocular surface status was assessed by Ocular Surface Disease Index (OSDI) symptom questionnaires, tear break-up time (BUT), fluorescein staining and the Schirmer test. Laser scanning in vivo confocal microscopy was applied to evaluate the LC density and morphology in both central and peripheral cornea. The correlations between confocal microscopy data and clinical data were also analyzed. RESULTS: The OSDI and fluorescein staining values were significantly higher, while BUT and Schirmer test scores were lower in both active and inactive TAO patients compared to the controls. Central LC densities of patients with active TAO (76.38 ± 67.77 cell/mm(2)) and inactive TAO (47.49 ± 38.58 cell/mm(2)) were both significantly higher than those of the controls (21.46 ± 21.74 cell/mm(2)). The number of LCs in the peripheral cornea was also significantly increased in the active TAO group (131.53 ± 74.18 cell/mm(2)) compared to the control group (70.21 ± 37.76 cell/mm(2)). Central LC morphology (LCM) values were significantly higher in both active (1.77 ± 0.63) and inactive (1.51 ± 0.63) TAO groups compared to the control group (1.01 ± 0.80), whereas peripheral LCM scores of the two TAO groups were increased without statistical significance. There were significant correlations between both central LC density and central LCM scores and clinical data, including clinical activity score, OSDI and Schirmer test scores, and between peripheral LC density and OSDI and Schirmer test scores. No significant correlations were found between peripheral LCM scores and clinical data. CONCLUSIONS: The increase of corneal LCs in density and maturation in patients with TAO reflects an activated state of the local immune system, which indicates an inflammatory process in the cornea of TAO.

Anti-vascular endothelial growth factor for control of wound healing in glaucoma surgery.

BACKGROUND: Trabeculectomy is performed as a treatment for glaucoma to lower intraocular pressure (IOP). The surgical procedure involves creating a channel through the wall of the eye. However scarring during wound healing can block this channel which will lead to the operation failing. Anti-vascular endothelial growth factor (VEGF) agents have been proposed to slow down healing response and scar formation. OBJECTIVES: To assess the effectiveness of anti-VEGF therapies administered by subconjunctival injection for the outcome of trabeculectomy at 12 months follow-up and to examine the balance of benefit and harms when compared to any other anti-scarring agents or no additional anti-scarring agents. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 12 November 2015. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of anti-VEGF therapies administered by subconjunctival injection compared to any other anti-scarring agents or no additional anti-scarring agents (no treatment or placebo) in trabeculectomy surgery. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcome was successful trabeculectomy at 12 months after surgery which was defined as achieving a target IOP (usually no more than 21 mm Hg) without any additional intervention. Other outcomes included: qualified success (achieving target IOP with or without additional intervention), mean IOP and adverse events. MAIN RESULTS: We included five RCTs (175 participants, 177 eyes) that met the inclusion criteria in this review.One trial conducted in Iran (37 participants, 37 eyes) compared anti-VEGF (bevacizumab 0.2 mg) versus control (sham injection) in people with refractory glaucoma. We judged this study to be at low risk of bias.The primary outcome of this review was not reported; mean IOP at three months was 15.1 mm Hg (standard deviation 1.0) in both anti-VEGF and control groups.Four trials compared anti-VEGF to mitomycin C (MMC) (138 particpants, 140 eyes). These studies were conducted in India, Iran, Turkey and the USA. The anti-VEGF agent used in these four trials was bevacizumab 2.5 mg (two trials), bevacizumab 1.25 mg three times and ranibizumab 0.5 mg. Two trials were at high risk of bias in two domains and one trial was at high risk of bias in four domains.Only one of these trials reported the primary outcome of this review (42 participants, 42 eyes). Low quality evidence from this trial showed that people receiving bevacizumab 2.5 mg during primary trabeculectomy were less likely to achieve complete success at 12 months compared to people receiving MMC but the confidence interval (CI) was wide and compatible with increased chance of complete success for anti-VEGF (risk ratio (RR) 0.71, 95% CI 0.46 to 1.08), Assuming that approximately 81% of people receiving MMC achieve complete success, the anticipated success using anti-VEGF agents would be between 37.2% and 87.4%. The same trial suggested no evidence for any difference in qualified success between bevacizumab and MMC (RR 1.00, 95% CI 0.87 to 1.14, moderate quality evidence). Two trials of primary trabeculectomy provided data on mean IOP at 12 months; one trial of bevacizumab 2.5 mg and one trial of ranibizumab 0.5 mg. Mean IOP was 1.86 mm Hg higher (95% CI 0.15 to 3.57) in the anti-VEGF groups compared to the MMC groups (66 people, low quality evidence). Data were reported on wound leak, hypotony, shallow anterior chamber and endophthalmitis, but these events occurred rarely and currently there are not enough data available to detect any differences, if any, between the two treatments. AUTHORS' CONCLUSIONS: The evidence is currently of low quality which is insufficient to refute or support anti-VEGF subconjunctival injection for control of wound healing in glaucoma surgery. The effect on IOP control of anti-VEGF agents in glaucoma patients undergoing trabeculectomy is still uncertain, compared to MMC.Further RCTs of anti-VEGF subconjunctival injection in glaucoma surgery are required, particularly compared to sham treatment with at least 12 months follow-up.

The Association Between Obstructive Sleep Apnea and Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is a multifactorial disease, and recently epidemiologic studies have investigated the association between obstructive sleep apnea (OSA) and NAION. A systematic review of the association of OSA and NAION has not been performed. Therefore, the current meta-analysis was performed to assess such potential association between OSA and risk of NAION. METHODS: A systematic search of PubMed and EMBASE databases was performed for published studies evaluating the association between OSA and NAION. The summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for categorical risk estimates. Sensitivity analyses and subgroup analyses were also performed to assess the robustness of pooled outcomes. RESULTS: A total of four prospective cohort studies and one case-control study met our inclusion criteria. The pooled OR of developing NAION in the subjects with OSA was 6.18 (95% CI, 2.00-19.11) versus non-OSA controls. Sensitivity analyses showed that no matter one study excluded, the pooled OR did not change significantly, which indicated that the evidence was robust. In subgroup analyses, a significant association was seen in studies matched systemic risk factors (OR, 5.00; 95% CI, 2.22-11.25), but not in those non-matched. The magnitude and direction of effects were also affected by methodological variability, including study design, and diagnosis of OSA. CONCLUSIONS: The findings from this meta-analysis supported the robust evidence that OSA was a strong independent risk factor of NAION. Relative to non-OSA controls, the subjects with OSA were found to have a more than sixfold risk of NAION. In future, more well-designed studies are needed to confirm these findings.

Common Immunosuppressive Monotherapy for Graves' Ophthalmopathy: A Meta-Analysis.

BACKGROUND: Several immunosuppressive therapeutic regimens are widely used to treat Graves' ophthalmopathy (GO), including oral glucocorticoids (OGC), intravenous glucocorticoids (IVGC), retrobulbar injections of glucocorticoids (ROGC) and orbital radiotherapy (OR). The priority among these is unknown. This meta-analysis investigated the efficacy and tolerability of the above regimens. METHODS: The PubMed, EMBASE, and Cochrane Library databases and the Chinese Biomedicine Database were searched up to November 18, 2014. Randomized controlled trials (RCTs) comparing monotherapies (OGC, IVGC, ROGC and OR) in patients with moderate-to-severe active GO were selected. The main efficacy measures were the response rate, the standard mean difference (SMD) in the reduction in the clinical activity score (CAS) and the mean difference (MD) in proptosis from baseline to the end of treatment. The main tolerability measure was the risk ratio (RR) for adverse events. The pooled estimates and 95% confidence intervals (95% CIs) were calculated using the RevMan software, version 5.1. RESULTS: Seven published RCTs involving 328 participants were included in the present meta-analysis, including IVGC versus OGC (3 trials), ROGC versus OGC (3 trials) and OR versus OGC (1 trial). IVGC was more effective than OGC in response rate (RR = 1.48, 95% CI = 1.18-1.87) and had an obvious CAS reduction (SMD = 0.69, 95% CI = 0.13-1.25). IVGC caused fewer adverse events than OGC. ROGC and OGC had no statistically significant difference in response rate (RR = 1.16, 95% CI = 0.94-1.42). OR also did not differ significantly compared with OGC (RR = 0.93, 95% CI = 0.54-1.60). ROGC and OR had fewer adverse events, such as weight gain, compared with OGC. CONCLUSIONS: For patients with GO in the moderate-to-severe active phase, current evidence gave priority to IVGC, which had a statistically significant advantage over OGC and caused fewer adverse events. ROGC and OR did not provide greater efficacy than OGC, although better tolerability and fewer adverse events were shown.

Loteprednol etabonate in the treatment of allergic conjunctivitis: a meta-analysis.

OBJECTIVE: This meta-analysis was designed to assess the efficacy, as well as the safety of loteprednol etabonate (LE) ophthalmic suspension compared with placebo and other commonly used eye drops for treatment of allergic conjunctivitis. METHODS: Comprehensive searches of randomized controlled trials were carried out in a database of Medline, Embase, and the Cochrane Library. Eight qualified studies were included. This study assessed the reduction from baseline in scores of cardinal signs and symptoms, proportion of patients with improvement of allergic signs and symptoms, and incidence of clinically significant intraocular pressure (IOP) elevation (IOP elevation ≥10 mmHg). RESULTS: The results showed that topical LE was significantly superior to placebo in reduction from baseline in signs scores (standardized mean difference [SMD] = -0.48; 95% confidence interval [CI] = -0.65 to -0.32) and symptoms scores (weighted mean difference [WMD] = -0.51; 95% CI = -0.64 to -0.38) of allergic conjunctivitis, and as effective as olopatadine and fluorometholone acetate. Topical LE was associated with a higher improvement rate of signs (risk ratio [RR] = 1.53; 95% CI = 1.26-1.86; I (2 )= 57%) and symptoms (RR = 1.29; 95% CI = 1.15-1.46; I (2 )= 54%) than placebo and the positive control treatment. Clinically significant IOP elevation was more frequent in the group of LE than the group of control treatment (pooled odds ratio = 3.03; 95% CI = 1.04-8.80), which was affected by the response to corticosteroid of the individual patient and the wearing of contact lenses. CONCLUSIONS: Topical LE is effective in treating allergic conjunctivitis. However, it should be used with caution due to the higher incidence of IOP elevation compared with placebo and olopatadine. A large-scale trial would be required to confirm the effect of different concentrations of LE on IOP.

Efficacy and tolerability of prostaglandin-timolol fixed combinations: an updated systematic review and meta-analysis.

BACKGROUND: Prostaglandin-timolol fixed combinations (PG-timolol FCs) are now widely used to reduce intraocular pressure in patients with glaucoma. The efficacy and tolerability of these drugs are worthy of further exploration. An updated systematic review and meta-analysis was performed to assess the clinical efficacy and tolerability of the three PG-timolol FCs. METHODS: Pertinent randomized, controlled trials were identified through systematic searches of PubMed, Embase, the Cochrane central register of controlled trials and the Chinese Biomedicine Database. The main efficacy measures were the weighted mean differences (WMDs) for the reduction from baseline to end of treatment in IOP at 9 am, 12 pm and 4 pm and diurnal curve. The main tolerability measures were the odds ratios (ORs) for the incidence of conjunctival hyperemia. RESULTS: Nine studies involving 991 patients were included in the meta-analysis. Latanoprost-timolol FC (LTFC) and travoprost-timolol FC (TTFC) were not significantly different in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm. Bimatoprost-timolol FC (BTFC) provided significantly greater efficacy in lowering IOP at the three measurement time points and over the mean diurnal curve than LTFC (diurnal curve: WMD = 0.88 mmHg [95% CI, 0.42 to 1.33]; 9 am: WMD = 1.27 mmHg [0.68 to 1.86]; 12 pm: WMD = 1.16 mmHg [0.85 to 1.46]; 4 pm: WMD = 0.61 mmHg [0.51 to 0.70]) and TTFC (diurnal curve: WMD = 1.94 mmHg [0.19 to 3.68]; 9 am: WMD = 0.68 mmHg [0.15 to 1.21]; 12 pm: WMD = 0.90 mmHg [0.41 to 1.39]; 4 pm: WMD = 1.06 mmHg [0.61 to 1.51]). The incidence of hyperemia was significantly higher with BTFC than LTFC (pooled ORs: 1.85 [1.09 to 3.13]). The incidence of hyperemia was not significantly higher with TTFC than LTFC (pooled ORs: 2.52 [0.85 to 7.46]), and was not significantly higher with BTFC than TTFC (pooled OR: 1.65 [0.48 to 5.70]). CONCLUSIONS: BTFC provided significantly greater efficacy in lowering IOP at diurnal mean, 9 am, 12 pm and 4 pm than LTFC and TTFC. LTFC was as effective as TTFC in lowering IOP at the four measurement time points and BTFC caused conjunctival hyperemia in more patients than LTFC. Further clinical trials are needed because of the limited number of studies.

CD40 ligand induces expression of vascular cell adhesion molecule 1 and E-selectin in orbital fibroblasts from patients with Graves' orbitopathy.

PURPOSE: The aim of this study was to detect the effect of the CD40 ligand (CD40L) on the expression of vascular cell adhesion molecule 1 (VCAM-1) and E-Selectin in orbital fibroblasts (OFs) from patients with Graves' orbitopathy (GO), as well as the signaling pathways involved in this effect. METHODS: OFs were isolated from orbital tissues obtained from patients with severe GO who were undergoing orbital decompression surgery. VCAM-1 and E-selectin RNA and protein expression levels were quantified in OFs stimulated with soluble CD40L (sCD40L). RNA and protein quantification was performed with real-time polymerase chain reaction (PCR) and western blot analysis. Cytoplasmic and nuclear fractions were isolated in order to detect the nuclear translocation of nuclear factor-κB (NF-κB). Signaling pathway inhibitors were applied to determine the pathways involved. RESULTS: Compared to unstimulated OFs, the mRNA and protein levels of VCAM-1 and E-selectin in OFs incubated with sCD40L were significantly increased. This was observed in dose- and time-course experiments, and the inductive effects of sCD40L were much weaker in OFs from healthy donors. At the same time, we observed that CD40L induced nuclear translocation of NF-κB, also in a dose- and time-dependent manner. The up-regulation of VCAM-1 and E-selectin, as well as the NF-κB nuclear translocation induced by CD40L, was significantly attenuated by inhibitors targeting mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3-kinase (PI3K), and NF-κB. CONCLUSIONS: CD40L demonstrated the ability to up-regulate the expression of VCAM-1 and E-selectin at the pre-translational level in OFs from patients with GO. The MAPK and PI3K pathways and NF-κB may play important roles in CD40L-induced VCAM-1 and E-selectin expression.

Meta-analysis of association between the +49A/G polymorphism of cytotoxic T-lymphocyte antigen-4 and thyroid associated ophthalmopathy.

PURPOSE OF THE STUDY: Cytotoxic-T lymphocyte antigen-4 (CTLA-4) has been shown to play an important role in the development and progression of thyroid associated ophthalmopathy (TAO). A number of case-control studies focused on the association between CTLA-4 +49A/G polymorphism and risk for TAO. But the results were not always consistent. So we performed a meta-analysis to evaluate the precise association between this polymorphism and risk for TAO. MATERIALS AND METHODS: All publications on the association between CTLA-4 +49A/G polymorphism and TAO were searched in the following electronic databases: PubMed, Embase, the Cochrane library and Chinese Biomedical Literature Database, with the last report up to May 2014. This meta-analysis was assessed by Review Manager 5.1. RESULTS: A total of 14 studies were involved in this meta-analysis, including 1128 cases and 2539 controls. Overall, we found a significant association between CTLA-4 +49A/G polymorphism and TAO (G versus A: OR = 1.64, 95% CI = 1.40-1.92, p < 0.00001; GG versus AG + AA: OR = 2.02, 95% CI = 1.59-2.57, p < 0.00001; GG + AG versus AA: OR = 2.01, 95% CI = 1.66-2.43, p < 0.00001; GG versus AA: OR = 2.74, 95% CI = 1.83-4.10, p < 0.00001; AG versus AA: OR = 1.75, 95% CI = 1.42-2.15, p < 0.00001). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded. Significant association was also detected in both Caucasian and Asian populations in subgroup analysis divided by different ethnicity. CONCLUSION: Our meta-analysis supports the association between the CTLA-4 +49A/G polymorphism and TAO.

The prevalence of primary angle closure glaucoma in adult Asians: a systematic review and meta-analysis.

BACKGROUND: Primary angle closure glaucoma (PACG) is higher in Asians than Europeans and Africans, with over 80% of PACG worldwide in Asia. Previous estimates of PACG were based largely on early studies, mostly using inappropriate case definitions. Therefore, we did a systematic review and meta-analysis to estimate the prevalence of PACG in adult Asian populations and to quantify its association with age, gender, and region. METHODS: All primary reports of population-based studies that reported the prevalence of PACG in adult Asian populations were identified. PACG case definition was compatible with the ISGEO definition. Twenty-nine population-based studies were included. The overall pooled prevalence estimates were calculated using a random effect model, and ethnicity-, age- and gender-specific pooled prevalence estimates were also calculated. RESULTS: The overall pooled prevalence of PACG in those of adult Asians was 0.75% (95% CI, 0.58, 0.96). Ethnicity-specific pooled prevalence estimates were 0.97% (0.22, 4.27) in Middle East group, 0.66% (0.23, 1.86) in South East Asia group, 0.46% (0.32, 0.64) in India group, 1.10% (0.85, 1.44) in China group, and 1.19% (0.35, 3.98) in Japan group, respectively. Age-specific prevalence was 0.21% (0.12, 0.37) for those 40-49 years, 0.54% (0.34, 0.85) for those 50-59 years, 1.26% (0.93, 1.71) for those 60-69 years, and 2.32% (1.74, 3.08) for those 70 years or above. The overall female to male ratio of the PACG prevalence was 1.51∶1 (95% CI 1.01, 2.28). CONCLUSIONS: PACG affects approximately 0.75% adult Asians, increasing double per decade, and 60% of cases being female. The prevalence rates vary greatly by ethnic region.

Meta-analysis of association between the -2578C/A polymorphism of the vascular endothelial growth factor and retinopathy in type 2 diabetes in Asians and Caucasians.

BACKGROUND AND OBJECTIVES: Vascular endothelial growth factor (VEGF) has been shown to play an important role in the development and progress of diabetic retinopathy (DR). A number of case-control studies focused on the association between VEGF -2578C/A and risk for DR. But the results were not always consistent, so we performed a meta-analysis to evaluate the precise association between this variant and risk for DR. METHODS: All publications on the association between VEGF -2578C/A polymorphism and DR were searched in the following electronic databases: PubMed, Embase, the Cochrane Library and Chinese Biomedical Literature Database, with the last report up to January 2013. This meta-analysis was assessed by Review Manager 5.1. RESULTS: A total of 6 studies were involved in this meta-analysis, including 835 cases and 867 controls. Overall, we found a significant association between this polymorphism and DR (A vs. C: OR=1.49, 95% CI=1.26-1.77, p<0.00001; AA vs. CA+CC: OR=1.26, 95% CI=0.94-1.68, p=0.12; AA+CA vs. CC: OR=1.56, 95% CI=1.27-1.91, p<0.00001; AA vs. CC: OR=1.67, 95% CI=1.20-2.32, p=0.003; CA vs. CC: OR=1.51, 95% CI=1.21-1.87, p=0.0002), but we did not find any significant association in Caucasians in subgroup analysis. The results were not materially altered after the studies which did not fulfill the Hardy-Weinberg equilibrium were excluded. CONCLUSION: Our meta-analysis supports the association between the VEGF -2578C/A polymorphism and DR, but not in the Caucasian population.

Efficacy and tolerability of latanoprost compared with timolol in the treatment of patients with chronic angle-closure glaucoma.

OBJECTIVE: To evaluate the efficacy and tolerability of latanoprost compared with timolol in the treatment of patients with chronic angle-closure glaucoma (CACG). METHODS: Pertinent publications were identified through systematic searches of PubMed, EMBASE, the Cochrane Controlled Trials Register and the Chinese Biomedicine Database. Randomized controlled trials comparing latanoprost with timolol in patients with chronic angle-closure glaucoma (CACG) who had inadequate intraocular pressure (IOP) control after peripheral iridotomy (PI) were selected. The main efficacy measures were the weighted mean difference (WMD) in the reduction from baseline to end of treatment in IOP at peak, trough, and diurnal curve. The main tolerability measures were the odds ratio (OR) for the individual adverse events. The pooled estimates and 95% confidence intervals (CIs) were carried out in RevMan version 5.2 software. RESULTS: Five published randomized controlled trials involving 528 patients were included in the present meta-analysis. The IOP reduction (IOPR) was significantly greater in the latanoprost group than in the timolol group at diurnal curve (WMD: 2.22 mmHg [95% CI, 1.65 to 2.79], P < 0.00001), peak (WMD: 2.44 mmHg [0.85 to 4.03], P = 0.003) and trough (WMD: 2.67 mmHg [1.93 to 3.41], P < 0.00001). Timolol caused conjunctival hyperemia in less patients than latanoprost (pooled OR: 2.74 [95% CI, 1.33 to 5.61], P = 0.006). CONCLUSIONS: Latanoprost provides greater IOP-lowering efficacy than timolol in the treatment of patients with CACG. Latanoprost caused conjunctival hyperemia in more patients than timolol. Further clinical trials are needed because of short duration of included studies.

Effect of intravitreal injection of bevacizumab-chitosan nanoparticles on retina of diabetic rats.

AIM: To investigate the effects of intravitreal injection of bevacizumab-chitosan nanoparticles on pathological morphology of retina and the expression of vascular endothelial growth factor (VEGF) protein and VEGF mRNA in the retina of diabetic rats. METHODS: Seventy-two 3-month aged diabetic rats were randomly divided into 3 groups, each containing 24 animals and 48 eyes. Both eyes of the rats in group A were injected into the vitreous at the pars plana with 3µL of physiological saline, while in groups B and C were injected with 3µL (75µg) of bevacizumab and 3µL of bevacizumab-chitosan nanoparticles (containing 75µg of bevacizumab), respectively. Immunohistochemistry was used to assess retinal angiogenesis, real-time PCR assay was used to analyse the expression of VEGF mRNA, and light microscopy was used to evaluate the morphology of retinal capillaries. RESULTS: Real-time PCR assay revealed that the VEGF mRNA expression in the retina before injection was similar to 1 week after injection in group A (P>0.05), while the VEGF mRNA expression before injection significantly differed from those 4 and 8 weeks after injection (P<0.05). Retinal expression of VEGF protein and VEGF mRNA was inhibited 1 week and 4 weeks after injection (P<0.05) in group B, and the expression of VEGF protein and VEGF mRNA was obviously inhibited until 8 weeks after injection (P<0.05) in group C. Using multiple comparisons among group A, group B, and group C, the VEGF expression before injection was higher than at 1, 4 and 8 weeks after injection (P<0.05). The amount of VEGF expression was higher 8 weeks after injection than 1 week or 4 weeks after injection, and also higher 1 week after injection compared with 4 weeks after injection (P<0.05). No toxic effect on SD rats was observed with bevacizumab-chitosan nanoparticles injection alone. CONCLUSION: The results offer a new approach for inhibiting angiogenesis of diabetic retinopathy and indicate that the intravitreal injection of bevacizumab inhibits VEGF expression in retina, and bevacizumab-chitosan nanoparticles have a longer duration of action.

Meta-analysis of selective laser trabeculoplasty with argon laser trabeculoplasty in the treatment of open-angle glaucoma.

OBJECTIVE: To evaluate the efficacy and tolerability of selective laser trabeculoplasty (SLT) and argon laser trabeculoplasty (ALT) in the treatment of open-angle glaucoma. DESIGN: Systematic review and meta-analysis. PARTICIPANTS: Six clinic studies, all of which were random controlled trials. METHODS: Pertinent studies were selected through extensive searches of PubMed, Cochrane Library, Embase, and meeting abstracts. Efficacy measures were weighted by mean differences for intraocular pressure (IOP), as well as change of number of glaucoma medications and relative risks (RRs) for therapeutic IOP responses. Tolerability measures were RRs for adverse events. Pooled estimates were carried out in RevMan software 5.1. RESULTS: SLT was associated with a numerically larger reduction compared with ALT, with a weighted mean difference (WMD) of 0.60 (95% CI, 0.06-1.14). There was no significant difference in therapeutic IOP responses between SLT and ALT, with a pooled RR of 0.84 (95% CI, 0.51-1.38). Patients who received SLT took fewer glaucoma medications after operations than those who received ALT, with a WMD of 0.29 (95% CI, 0.01-0.56). When compared in patients with previous failed laser treatment (ALT or SLT), SLT was more effective in IOP reduction than ALT with a WMD of 1.48 (95% CI, 0.75-2.21). The frequencies of anterior chamber flare and IOP peak after operation were similar comparing SLT and ALT, with pooled RRs of 0.90 (95% CI, 0.74-1.11) and 0.90 (95% CI, 0.45-1.82), respectively. CONCLUSIONS: SLT was associated with relatively higher efficacy of IOP lowering compared with ALT. SLT results in a larger reduction of number of glaucoma medications versus ALT, and it appeared to be more effective for patients who did not respond adequately to previous laser treatment. The difference in tolerability of the 2 lasers was not significant.

Efficacy and tolerability of fixed combination of brimonidine 0.2%/timolol 0.5% compared with fixed combination of dorzolamide 2%/timolol 0.5% in the treatment of patients with elevated intraocular pressure: a meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and tolerability of the fixed-combination brimonidine 0.2%/timolol 0.5% (FCBT) compared with the fixed-combination dorzolamide 2%/timolol 0.5% (FCDT) in the treatment of patients with elevated intraocular pressure (IOP). METHODS: Pertinent randomized controlled trials comparing FCBT with FCDT in patients with elevated IOP were identified through systematic searches of the Cochrane Library, PubMed, and EMBASE. The main efficacy measures were the IOP reduction (IOPR), including diurnal mean IOPR, and peak IOPR. The main tolerability measure was the individual adverse events. The pooled estimates and 95% confidence intervals (CIs) were carried out in RevMan version 5.0 software. RESULTS: Seven studies involving 582 patients were included in the meta-analysis. With a weighted mean difference (WMD) of IOPR in diurnal mean of 0.44 mmHg (95% CI, 0.00-0.88), the FCBT was as effective as FCDT in lowering IOP in patients with elevated IOP (P=0.05). The WMD of IOPR at peak was 0.65 mmHg (95% CI, -0.06 to 1.35) (P=0.76), and there was no significant difference between FCBT and FCDT. FCBT caused burning/stinging in less patients than FCDT [pooled relative risk: 0.45 (95% CI, 0.29-0.70)]. CONCLUSIONS: Both FCBT and FCDT can effectively lower IOP in patients with elevated IOP, and the IOP-lowering efficacy of FCBT is noninferior to that of FCDT. Additionally, FCBT affords an ocular comfort advantage compared with FCDT.