Changes in retinal nerve fibre layer, ganglion cell layer and visual function in eyes with thyroid eye disease of different severities with and without orbital decompression.

PURPOSE: To evaluate progressive changes in retinal nerve fibre layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL) and visual function in thyroid eye disease (TED) patients with and without orbital decompression. METHODS: Sixty TED patients (105 eyes) were included. All patients were divided into mild, moderate-to-severe and dysthyroid optic neuropathy (DON) groups. Orbital decompression was performed in the moderate-to-severe and DON groups. Optic coherence tomography (OCT), visual field (VF) and best-corrected visual acuity (BCVA) were performed pre- and postoperatively. Preoperative follow-up was performed in the mild group and in part of the moderate-to-severe and DON groups. RESULTS: After decompression, the thickness of GCL/IPL and RNFL significantly decreased in DON group (p < 0.05), with varying degrees of decrease in eyes with optic disc swelling, atrophy and normal appearance. The mean GCL/IPL thickness significantly decreased in moderate-to-severe group (p < 0.05), the mean RNFL thickness slightly decreased with no statistical significance (p = 0.07). During the preoperative follow-ups, the mean GCL/IPL thickness significantly decreased (p = 0.04), whereas the mean RNFL thickness tended to increase (p = 0.13) in DON group. The thickness of GCL/IPL and RNFL did not change significantly in the mild and moderate-to-severe groups (p > 0.05). BCVA and VF did not change significantly in any group (p > 0.05) preoperatively. CONCLUSION: Swelling and degeneration of retinal ganglion cells (RGCs) may coexist in DON eyes, leading to continuous changes in the RNFL and GCL/IPL thickness either before or after decompression. Slight swelling and degeneration of RGCs may exist in moderate-to-severe TED eyes, although OCT measurements and visual functions remain stable before surgery.

Ultra-low-dose radiotherapy in the treatment of ocular adnexal lymphoma: a prospective study.

PURPOSE: This single-arm, prospective, exploratory study investigated the effectiveness of ultra-low-dose radiotherapy in the treatment of ocular adnexal lymphoma (OAL). PATIENTS AND METHODS: Patients with pathologically confirmed ocular adnexal low-grade non-Hodgkin lymphoma (predominantly mucosa-associated lymphoid tissue, MALT or follicular lymphoma) were included and treated with ultra-low-dose radiotherapy consisting of 2 successive fractions of 2 Gy at our institution between 2019 and 2021. Disease response was assessed clinically and radiographically within 4 months and at 3 to 6-month intervals after treatment. Data collected included rates of overall response, complete response (CR), partial response (PR), lesion size, and acute/chronic ocular toxic effects. RESULTS: Sixteen patients with median age of 63 years (range 23-86 years) were included in the study. The histological subtypes included MALT (11 patients; 69%); follicular lymphoma (2 patients; 12%); Lymphoid hyperplasia (3 patient, 19%). At a median follow-up time of 15.5 months (range 5.0-30.0 months), the overall response rate was 88%, with a CR rate of 75% (n = 12) and a PR rate of 13% (n = 2). The average lesion area was reduced from 117.9 ± 60.4 mm2 before radiation therapy to 38.7 ± 46.0mm2 at initial evaluation post radiation therapy (P = 0.002, n = 16), and to 8.5 ± 21.2 mm2 (P < 0.001 compared with postoperative lesion area) in patients with response at one year (n = 11). Disease progression was noted in 2 patients (12%). The 1-year rates of local progression-free survivals (LPFS) and overall survival (OS) were 85% and 100%, respectively. No distant relapses were observed in any of the patients. No acute or late toxic effects were noted. CONCLUSION: Ultra-low-dose radiotherapy in patients with OAL is associated with excellent local disease control and long-term survival with no significant acute or late toxicities.

Quantitative T1 mapping MRI for the assessment of extraocular muscle fibrosis in thyroid-associated ophthalmopathy.

PURPOSE: We aimed to investigate the performance of T1 mapping and its histological correlation with extraocular muscle fibrosis in thyroid-associated ophthalmopathy (TAO). METHODS: We prospectively recruited 12 cases of active TAO, 12 cases of inactive TAO, and 15 cases of control subjects. All participants underwent magnetic resonance imaging (MRI) scan with pre-/postcontrast T1 mapping and short-time inversion-recovery (STIR) sequence. The images were analyzed to obtain precontrast T1, extracellular-volume (ECV) fraction on T1 mapping, and signal-intensity ratio (SIR) on STIR for each rectus. Muscle biopsy was performed at lateral rectus to quantify-collagen volume fraction, glycosaminoglycan (GAG)-volume fraction, and extracellular space component. The relationship between MRI and histopathology was examined with Pearson correlation coefficient. RESULTS: The active TAO group was characterized with GAG accumulation, while the inactive TAO group presented with substantial fibrosis. The MRI parameters achieved acceptable interobserver and intraobserver agreement. The precontrast T1 and ECV remarkably increased in the TAO groups than the control group, and ECV positively correlated with collagen-volume fraction (r = 0.913) and extracellular-space component (r = 0.886) in the inactive TAO group. The SIR statistically increased in the active TAO group, and SIR positively correlated with GAG-volume fraction in all three groups. The performance of ECV (cutoff > 48.1%) to screen out extraocular muscle fibrosis in inactive TAO was 60.9% sensitivity and 93.3% specificity. CONCLUSIONS: The ECV parameter on T1 mapping MRI is a reliable tool to quantify extraocular muscle fibrosis, providing insights into noninvasive evaluation of pathological changes in TAO orbit. TRIAL REGISTRATION NUMBER: ChiCTR2000040394; Date of registration: 28 November 2020.

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.

The Efficacy of Conbercept in Polypoidal Choroidal Vasculopathy: A Systematic Review.

METHODS: Thirty studies with 1308 eyes were identified and included in this study. The primary outcome measures were best-corrected visual acuity (BCVA), and secondary outcomes were optical coherence tomography characteristics and polyp regression rates. The pooled results were calculated by the random-effect or fixed-effect model according to the heterogeneity of the data. RESULTS: Despite a large standard deviation in means (SMD) improvement for BCVA and central retinal thickness (CRT) in the conbercept group, there was no statistically significant difference in the other outcomes compared to ranibizumab and aflibercept. However, there was a greater polyp regression rate in the conbercept group at 12 months. CONCLUSIONS: This systematic review indicates that conbercept may achieve similar BCVA and CRT improvements as ranibizumab and aflibercept, with a superior rate of polyp regression at 12 months.

Bilateral cellulitis caused by invasive aspergillosis associated with bilateral intraorbital abscesses: a case report.

BACKGROUND: Orbital invasive aspergillosis infection is rare life-threatening infection, most commonly seen in immunocompromised patients and extremely rare in individuals without risk factors. Here we present a rare case of bilateral cellulitis caused by invasive aspergillosis associated with bilateral intraorbital abscesses in a female patient. CASE PRESENTATION: A 49-year-old woman presented with a 3-month history of painful proptosis and periorbital swelling of bilateral eyes. She was initially diagnosed as bilateral orbital cellulitis complicated with cavernous sinus thrombosis and was treated with antibiotic medication for 1 month, but her symptoms persisted. MRI demonstrated orbital masses behind both globes. The lesion in right orbit was biopsied with a diagnosis of orbital granulomatosis with invasive aspergillosis infection. The patient was healed after receiving antifungal treatment. CONCLUSIONS: This is an unusual case about bilateral orbital abscesses with invasive fungal infection. Fungal infection of the orbit should be considered when patient does not respond to combination of anti-inflammatory and antibiotic therapies, even in some cases without any risk factors.

Solitary fibrofolliculoma of the upper eyelid in a 68-year old female: a case report.

BACKGROUND: Fibrofolliculoma is a benign, perifollicular, connective tissue tumor, and it usually arises in the form of multiple lesions, but rarely as a solitary lesion. We report a case of solitary fibrofolliculoma on the eyelid. CASE PRESENTATION: A 68-year-old female presented with an asymptomatic mass on the right upper eyelid. The lesion appeared as a flesh-colored, dome-shaped, smooth nodule being the size of 5 × 5 × 4 mm, with eyelashes protruding from the surface, and located on the upper lid margin. Shave excision was performed, and the diagnosis of fibrofolliculoma was confirmed finally through histological exam. CONCLUSIONS: Solitary fibrofolliculomas rarely arises on the eyelid. However, it should be suspected when a flesh-colored and doom-shaped lesion of the eyelid is encountered. The benign tumor on the lid margin can be removed by shave biopsy.

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.

Up-Regulated ATF4 Expression Increases Cell Sensitivity to Apoptosis in Response to Radiation.

BACKGROUND/AIMS: Activating transcription factor 4 (ATF4) is a member of the activating transcription factor family which regulates the expression of genes involved in amino acid metabolism, redox homeostasis and ER stress responses. ATF4 is also over-expressed in human solid tumors, although its effect on responsiveness to radiation is largely unexplored. METHODS: Real-time PCR was used to detect ATF4 mRNA levels in cells treated with different doses of 60Coγ radiation. Cell viability was assayed using a cell counting kit. The cell cycle was analyzed using flow cytometry, and cell apoptosis was assayed using Annexin V-PI double labeling. Small interfering RNA (siRNA) against ATF4 was transfected into ECV304 cells using Lipofectamine 2000. An ATF4 over-expression plasmid (p-ATF4-CGN) was transfected into HEK293 cells that endogenously expressed low levels of ATF4. The levels of intracellular reactive oxygen species (ROS) were measured using CM-H2DCFDA as a probe. RESULTS: ATF4 mRNA and protein expression levels were higher after radiation and increased in a dose- and time-dependent manner in AHH1 lymphoblast cells (P < 0.05). An increase in ATF4 levels was also observed after radiation in primary murine spleen cells, human endothelial ECV304 cells, human liver LO2 cells, breast cancer MCF7 cells, and human hepatocellular carcinoma HEPG2 cells. No change was observed in human embryonic kidney 293 (HEK293) cells. Over-expressing ATF4 in HEK293 cells inhibited cell proliferation, increased cell apoptosis and significantly increased the proportion of cells in G1 phase. Conversely, when ATF4 expression was knocked down using siRNA in ECV304 cells, it protected the cells from radiation-induced apoptosis. These findings suggest that ATF4 may play a role in radiation-induced cell killing by inhibiting cell proliferation and promoting cell apoptosis. CONCLUSIONS: In this study, we found that radiation up-regulated the expression of ATF4. We used ATF4 knockdown and over-expression systems to show that ATF4 may play a role in radiation-induced cellular apoptosis.

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.

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.

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 -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.

Sustained release of 5-fluorouracil from chitosan nanoparticles surface modified intra ocular lens to prevent posterior capsule opacification: an in vitro and in vivo study.

PURPOSE: The study aimed to prepare a new type intra ocular lens (IOL), in which 5-Fu, as an antimetabolite drug, could be sustained released to prevent posterior capsule opacification (PCO), and evaluate its efficacy and safety in vitro and in vivo. METHODS: 5-fluorouracil chitosan nanoparticles (5-Fu-CSNP) were prepared by template polymerization and selected by a cell counting kit (CCK-8). The 5-Fu-CSNPs that inhibit Human Lens Epithelial Cells (HLECs) proliferation most efficiently were chosen for further analysis. We then investigated cell death type in vitro by flow cytometry and fluorescent probe. IOLs were surface modified by 5-Fu-CSNP after being activated by a low energy fluorine ion beam, and then were implanted into rabbits' eyes after transparent lens enucleation to evaluate the efficacy of preventing PCO and safety in anterior chamber. Transparency and haze of the 5-Fu-CSNP-surface-modified intraocular lens (Nano-5-Fu-IOL) were detected by a haze meter. Drug release of the Nano-5-Fu-IOL was measured by UV spectrophotometry. RESULTS: The CCK results showed that the half inhibition dose (ID50) of the HLECs in 5-Fu-CSNP group and in 5-Fu solution group was 0.2 µg/mL and 1 µg/mL, respectively. The transparency of the 5-Fu-CSNP modified IOL was observed to have no significant difference with the blank control. The IOLs can continuously release 5-Fu in 4 days in vitro. In vivo, 5-Fu-CSNP IOL group had little aqueous flare 3 days after the surgery, and lighter PCO 4 weeks after the surgery than the blank control group. The results of the light microscope and electron microscope further confirmed the above results in vivo. CONCLUSIONS: The new IOL modified by 5-Fu-CSNP could be prepared and have a sustained release of 5-Fu to prevent PCO by promoting HLEC apoptosis. The drug-loaded CSNP could reduce the anterior chamber toxicity of 5-Fu markedly, which was probably due to the occurrence of endoplasmic reticulum stress and induction of apoptosis.

[Analysis of clinical features in distensible orbital venous malformations].

OBJECTIVE: To study the characteristic of the clinical and image features of distensible orbital venous malformations (DOVM). METHODS: It was a retrospective case series study. Clinical features and imaging findings, including B ultrasonography, CDFI, MRI, CT imaging of 43 patients with DOVM were reviewed in Shanghai Changzheng Hospital affiliated to Secondary Military Medical University RESULTS: Forty-three patients (24 women and 19 men), whose ages range from 5 to 71 years old, showed clinical or radiological evidence of distensibility. The mean age was 32 years. Location of the lesion within the orbit was variable, 9 patients with superficial lesions, and 19 patients with deep lesions. Twelve patients were classified as combined lesions. 3 patients with extraorbital venous malformations were classified as complex lesions. Twenty of 43 patients with DOVM were initially seen with proptosis or pain increasing with the head in a dependent position. Eight patients presented with a sudden onset of proptosis and pain secondary to thrombosis or hemorrhage. B ultrasonography showed an intermittently anechoic lesion that exhibits intrinsic flow during the Valsalva maneuver. Color Doppler imaging might demonstrate a reversal of flow toward the transducer during the Valsalva maneuver. Thirty-five of 43 cases with axial CT images showed a normal appearance or only mild enlargement of the involved veins, but coronal CT images could clearly demonstrate the lesion distensibility. Eight cases showed well defined tumor with homogeneous high density due to the thrombosis or hemorrhage within the orbit. MR imaging showed hypo to hyperintense signal on T(1)-weighted images, had hyperintense signal on T(2)-weighted MR images. However, signal of lesions of orbital hemorrhage could be various according to the different hemorrhage time. CONCLUSION: DOVM usually occurs in young patients. Clinical diagnosis can be established with the typical symptoms and one or more imaging examinations.

Association of GSTP1 Ile105Val polymorphism and risk of head and neck cancers: a meta-analysis of 28 case-control studies.

BACKGROUND AND AIMS: The Glutathione S-transferase P1 (GSTP1) polymorphism have been considered a risk modifier for developing head and neck cancer (HNC) in many studies; however, the results of such studies are inconsistent. The aim of this study was to evaluate the possible association between the GSTP1 Ile105Val polymorphism and risk of HNC. METHOD: We performed a search in the relevant electronic database and a meta-analysis based on 28 published case-control studies that included 6,404 cases and 6,523 controls. To take into account the possibility of heterogeneity across the studies, a Chi-square based I(2)-statistic test was performed. Crude pooled odds ratios (ORs) with 95% confidence intervals (CIs) were assessed using both fixed-effects and random-effects models. RESULTS: The results of this meta-analysis showed that the GSTP1 Ile105Val polymorphism was not significantly associated with risk of HNC in the overall study population (pooled OR 1.00, 95% CI 0.92-1.09) or in subgroup analyses stratified by ethnicity, sample size, tumor site or publication year. Moreover, substantial evidence of heterogeneity among the studies was observed. Publication year was identified as the main cause of heterogeneity. CONCLUSION: This meta-analysis does not support a significant association between the GSTP1 Ile105Val polymorphism and risk of HNC.

Effect of intravitreal anti-vascular endothelial growth factor therapy on the risk of arterial thromboembolic events: a meta-analysis.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (VEGF) monoclonal antibodies are used in ocular neovascular diseases. A consensus has emerged that intravenous anti-VEGF can increase the risk of arterial thromboembolic events. However, the role of intravitreal anti-VEGF in arterial thromboembolism is controversial. Therefore, we did a systematic review and meta-analysis to investigate the effects of intravitreal anti-VEGF on the risk of arterial thromboembolic events. METHODS: Electronic databases were searched to identify relevant randomized clinical trials comparing intravitreal anti-VEGF with controls. Criteria for inclusion in our meta-analysis included a study duration of no less than 12 months, the use of a randomized control group not receiving any intravitreal active agent, and the availability of outcome data for arterial thromboembolic events, myocardial infarction, cerebrovascular accidents, and vascular death. The risk ratios and 95% CIs were calculated using a fixed-effects or random-effects model, depending on the heterogeneity of the included studies. RESULTS: A total of 4942 patients with a variety of ocular neovascular diseases from 13 randomized controlled trials were identified and included for analysis. There was no significant difference between intravitreal anti-VEGF and control in the risk of all events, with risk ratios of 0.87 (95% CI, 0.64 to 1.19) for arterial thromboembolic events, 0.96 (95% CI, 0.55-1.68) for cerebrovascular accidents, 0.69 (95% CI 0.40-1.21) for myocardial infarctions, and 0.68 (95% CI, 0.37-1.27) for vascular death. CONCLUSIONS: The strength evidence suggests that the intravitreal use of anti-VEGF antibodies is not associated with an increased risk of arterial thromboembolic events.

Lack of association of conjunctival MALT lymphoma with Chlamydiae or Helicobacter pylori in a cohort of Chinese patients.

BACKGROUND: This study was conducted to detect microbial pathogens in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma specimens in an attempt to determine possible associations between conjunctival MALT lymphoma and microbial infections. MATERIAL/METHODS: Using PCR technique, freshly obtained tumor specimens from 16 cases of conjunctival MALT lymphoma, as confirmed by postoperative pathology, were analyzed for DNA of Chlamydia psittaci (C. psittaci), Chlamydia trachomatis (C. trachomatis), Chlamydia pneumoniae (C. pneumoniae) and Helicobacter pylori (H. pylori). Synthetic C. psittaci, C. trachomatis, C. pneumoniae and H. pylori DNA were used as positive control, and blank plasmid DNA as negative control. RESULTS: Electrophoresis showed that no bands corresponding to the positive control were observed in the specimens, indicating that no DNA of the 4 microorganisms was detected in the specimens of the 16 cases of conjunctival MALT lymphoma. CONCLUSIONS: The PCR technique was able to detect the positive control quickly and accurately, but the results of PCR in analyzing the 16 specimens were negative, indicating that there is no association between conjunctival MALT lymphoma and the 4 microorganisms in Chinese patients.

MicroRNA-200 is commonly repressed in conjunctival MALT lymphoma, and targets cyclin E2.

BACKGROUND: Aberrant microRNA expression is implicated in cancer initiation and progression. We sought to identify dysregulated miRNAs in conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma, and investigated their biological significance. METHODS: The profiles of miRNAs in conjunctival MALT lymphoma and normal adjacent tissues were investigated by microRNA microarray of four pairs of surgically removed conjunctival MALT lymphoma tissues and matched controls. The results of microarray were further confirmed in 14 paired conjunctival MALT lymphoma samples (including the former four pairs) using quantitative RT-PCR. The functional effect of miR-200 was examined further. A luciferase reporter assay was performed to confirm the predicted target. RESULTS: The microarray results revealed upregulated miR-150/155, and downregulated miR-184, miR-200a, b, c, and miR-205. These findings were confirmed by quantitative RT-PCR. Targetscan analysis suggested cyclin E2 as potential target of miR-200a, b, c. Luciferase reporter assay using vectors containing the 3'UTR of cyclin E2 showed that miR-200a, b, c could suppress luciferase activities. RT-PCR and immunoblotting studies revealed that overexpression of miR-200a, b, c reduced the mRNA and protein levels of cyclin E2 respectively. CONCLUSIONS: We demonstrated that miRNAs were dysregulated in conjunctival MALT lymphoma, and dysregulation of the miR-200 family could be involved in the pathogenesis and progression of the disease.