Qingyu Liu

Steroids as an adjunct for reducing the incidence of proliferative vitreoretinopathy after rhegmatogenous retinal detachment surgery: a systematic review and meta-analysis.

Background This meta-analysis was performed to determine the effectiveness of steroids as an adjunct following rhegmatogenous retinal detachment (RRD) surgery. Methods RRD patients with or without proliferative vitreoretinopathy (PVR) were included. The treatment group included patients in whom steroids were used as an adjunct and a control group in which placebo was used. Only randomized controlled trials were included. We searched the main electronic databases and included studies published until July 2014. PVR odds ratio, visual acuity, retinal reattachment rate, and complications were evaluated in three trials. Results Three randomized controlled trials were included in the meta-analysis. There was no significant difference in the incidence of postoperative PVR between groups (heterogeneity I2=48%, P=0.14). However, the incidence of postoperative PVR was lower in the treatment group (I2=0%, P<0.0001) than in the control group when a PVR grade C study was excluded. There was no statistically significant difference in postoperative visual acuity between the treatment and control groups (odds ratio −0.18; 95% confidence interval −0.38, 0.02; P=0.08). The two groups had similar results for primary/final retinal reattachment and reoperation rate. There was no significant difference in postoperative intraocular pressure. Conclusion This systematic review demonstrates that steroids may significantly reduce the incidence of postoperative PVR grade B or lower following RRD surgery.

Proteomic analysis of tears following acupuncture treatment for menopausal dry eye disease by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry

Background The purpose of this study was to investigate whether acupuncture is effective at treating dry eye disease among postmenopausal women and to identify the possible mechanisms. Methods Twenty-eight postmenopausal women with dry eye disease were randomly divided into two groups: an acupuncture plus artificial tears (AC + AT) group and an artificial tears (AT) only group. After baseline examination of clinical parameters and tear sample collection, each patient received the designated modality of topical therapy for 2 months. Post-treatment documentation of clinical parameters was recorded, and tear samples were collected. Tear samples from the AC + AT group were subjected to two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry (2D nano-LC-MS/MS). Western blot analysis was also performed on tear samples from both groups. Results After treatment, the Ocular Surface Disease Index scores, symptom assessment scores, scores of sign assessment, and tear break-up time were significantly improved in both groups (P=0.000). Symptom assessment scores were significantly improved in the AC + AT group (P=0.000) compared with the AT group. 2D nano-LC-MS/MS identified 2,411 proteins, among which 142 were downregulated and 169 were upregulated. After combined AC + AT treatment, the abundance of secreted proteins was increased, whereas that of cytoplasmic proteins decreased (Pearson’s χ2 test, P=0.000, P=0.000, respectively). Proteins involved in immunity and regulation were also more abundant (Pearson’s χ2 test, P=0.040, P=0.016, respectively), while components and proliferation-related proteins were downregulated (Pearson’s χ2 test, P=0.003, P=0.011, respectively). Conclusion AC + AT treatment increased protein synthesis and secretion, and improved clinical symptoms. These results indicate that acupuncture may be a complimentary therapy for treating postmenopausal dry eye disease.

Circulating miRNAs as Potential Biomarkers of Age-Related Macular Degeneration

Backgroud: Age-related macular degeneration (AMD) is one of the leading causes of irreversible blindness of the elder people. This research was intended to demonstrate the different expression of microRNAs (miRNA) in AMD patients and whether they can be used as biomarkers for AMD. Methods: MiRNAs expression was measured by microarray of 6 AMD cases and 6 gender matched controls. In a larger-sample case-control study with 126 AMD cases and 140 controls, whole blood samples were detected for the differences of miRNA expression. Results: A total of 216 differentially expressed miRNAs (111 increased and 105 decreased miRNAs) were detected from circulating miRNA microarray. Expanded case-control study results showed that the expression of miR-27a-3p, miR-29b-3p and miR-195-5p was increased significantly. Moreover, the level of miR-27a is higher in patients with wet AMD compared to patients with dry AMD. All 3 miRNAs showed a potential diagnostic value for AMD. Conclusion: Circulating miRNA levels were significantly varied in AMD patients. Three miRNAs, miR-27a-3p, miR-29b-3p and the miR-195-5p, might be potential diagnostic biomarkers for AMD.

Effects of bradykinin on TGF‑β1‑induced epithelial‑mesenchymal transition in ARPE‑19 cells

The aim of the present study was to investigate the effects of bradykinin (BK) on an epithelial-mesenchymal transition (EMT) model in retinal pigment epithelium (RPE) cells through exposure to transforming growth factor-β1 (TGF-β1). The aim was to improve the effect of BK on proliferative vitreoretinopathy (PVR) progression, and to find a novel method of clinical prevention and treatment for PVR. The morphology of ARPE-19 cells was observed using an inverted phase-contrast microscope. A Cell Counting Kit-8 was used to assess the effects of TGF-β1 on the proliferation of ARPE-19 cells. Western blotting and immunofluorescence were used to detect the expression levels of the epithelial marker E-cadherin, mesenchymal markers α-smooth muscle actin (SMA) and vimentin, and phosphorylated (p) mothers against decapentaplegic homolog (Smad)3 and Smad7 of the TGF/Smad signaling pathway. Wound healing tests and Transwell assays were performed to detect cell migration ability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the expression levels of pSmad3 and Smad7 in the TGF/Smad signaling pathway. The results revealed that the addition of 10 ng/ml TGF-β1 resulted in the expression of factors associated with EMT in ARPE-19 cells. BK decreased the expression levels of the mesenchymal markers α-SMA and vimentin, and increased the expression of the epithelial marker E-cadherin. BK decreased cell migration in TGF-β1-induced EMT. These effects were reversed by HOE-140, a specific BK 2 receptor antagonist. BK significantly downregulated the expression of pSmad3 and upregulated the expression of Smad7 in TGF-β1-treated ARPE-19 cells, and the protective alterations produced by BK were inhibited by HOE-140. In conclusion, 10 ng/ml TGF-β1 resulted in EMT in ARPE-19 cells and BK served a negative role in TGF-β1-induced EMT. BK had effects in TGF-β1-induced EMT by upregulating the expression of Smad7 and downregulating the expression of pSmad3 in TGF-β/Smad signaling pathway, indicating that BK may be a novel and effective therapy for PVR.

Combination of bevacizumab and photodynamic therapy vs. bevacizumab monotherapy for the treatment of wet age‑related macular degeneration: A meta‑analysis of randomized controlled trials

The purpose of this meta-analysis was to compare the efficacy and safety of the combination of bevacizumab and photodynamic therapy (PDT) with bevacizumab monotherapy for the treatment of age-related macular degeneration (AMD). Patients with active choroidal neovascularization (CNV) secondary to AMD were included in the present study. The treatment group included patients treated with a combination of bevacizumab and PDT and patients treated with bevacizumab monotherapy. Only randomized controlled trials (RCTs) were included in the analysis. The PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases were searched. Meta-analysis was performed using RevMan v.5.3 software, and best-corrected visual acuity (BCVA), central retinal thickness (CRT) and the average number of bevacizumab retreatments were assessed. A total of 5 RCTs were included in the analysis. There were no significant differences observed in the mean BCVA change between the combination treatment group and the bevacizumab monotherapy group [standard mean difference 0.20; 95% confidence interval (CI) −0.53, 0.93, P=0.59]. There were also no significant differences in the CRT increases between the two groups [weighted mean difference (WMD) −22.16, 95% CI −52.01 to 7.69, P=0.15]. No significant differences were observed in the proportions of patients gaining >15 letters between the two groups [risk ratio (RR) 0.86, 95% CI 0.64, 1.15, P=0.30]. However, the average number of the ranibizumab retreatments was significantly lower in the combination treatment group compared with the bevacizumab monotherapy group (WMD, −2.70, 95% CI −3.93 to −1.46; P<0.0001). Additionally, there were no significant differences in the rate of ocular adverse events (RR, 0.57; 95% CI, 0.27 to 1.22; P=0.15) and systemic adverse events (RR, 5.42; 95% CI, 0.29 to 101.77; P=0.26) between the two groups. In conclusion there were no significant differences in mean BCVA change, CRT increases, the proportions of patients gaining >15 letters, or the incidences of ocular adverse events and systemic adverse events. However, combination treatment may significantly reduce the average number of bevacizumab retreatments compared with monotherapy.

The Effect of CM082, an Oral Tyrosine Kinase Inhibitor, on Experimental Choroidal Neovascularization in Rats

The aims of this study were to evaluate the effects of CM082 on the development of choroidal neovascularization (CNV) in a laser-induced CNV rat model and to determine the drug concentration in the ocular tissues. After the laser-induced CNV model was established in rats, CM082 was orally administered. The effects of CM082 on the CNV lesions were assessed using fundus fluorescein angiography (FFA), CNV histology, and retinal pigment epithelium- (RPE-) choroid-sclera eyecup analysis. The concentrations of CM082 in the plasma and eye tissues were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results of FFA, histology, and RPE-choroid-sclera eyecup analysis demonstrated that the CM082-treated (10 mg/kg/d or 30 mg/kg/d) rats exhibited significantly less neovascularization than did the control group. The total concentration of CM082 in the eyes (172.86 ± 57.11 ng/g) was similar to that in the plasma (196.87 ± 73.13 ng/ml). Within the eye, the concentrations of CM082 and its metabolites were highest in the retina-sclera. The orally administered CM082 thus effectively passed through the blood-retina barrier (BRB) to reach the retina in the Brown Norway rats. Therefore, at both 10 mg/kg/d and 30 mg/kg/d, CM082 was able to reduce CNV lesions in the laser-induced CNV rat model.

Efficacy and safety of different doses of a slow-release corticosteroid implant for macular edema [Corrigendum]

[This corrects the article on p. 2527 in vol. 9.].

Effect of bradykinin on TGF-β1-induced retinal pigment epithelial cell proliferation and extracellular matrix secretion

BackgroundTo evaluate the effect of bradykinin (BK) on TGF-β1-induced retinal pigment epithelial (RPE) cell proliferation and extracellular matrix secretion and to elucidate the relationship between BK and the Erk/Akt signaling pathway.MethodsThe effects of BK on TGF-β1-induced RPE cell proliferation were examined via CCK-8 assay. Cell culture supernatant collagen I concentrations were measured via ELISA. Fibronectin (Fn), matrix metalloproteinase-2 (MMP-2) and MMP-9 mRNA and protein expression levels were measured via q-PCR and Western blotting, respectively. Changes in Akt/Erk phosphorylation induced by BK and HOE-140 were evaluated via Western blotting.ResultsTGF-β1 stimulated ARPE-19 cell proliferation, which was inhibited by BK, whose effects were inhibited by HOE-140. BK inhibited TGF-β1-induced collagen I, Fn and MMP-2 secretion in RPE cells, and these effects were inhibited by HOE-140. BK also inhibited TGF-β1-induced Akt phosphorylation in RPE cells, and these effects were blocked by HOE-140. BK had no significant effect on Erk-mediated signaling.ConclusionsThe findings from this study indicate that BK could be novel therapeutic targets for the treatment of PVR.

Efficacy and safety of different doses of a slow-release corticosteroid implant for macular edema: meta-analysis of randomized controlled trials

Background The purpose of this meta-analysis was to assess the efficacy and safety of intravitreal corticosteroid implants for macular edema. Methods A total of 3,586 patients from previously reported randomized controlled trials were included. The meta-analysis was performed using RevMan 5.2. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, employing random-effects or fixed-effects models according to between-study heterogeneity. The main outcome measures were the ORs for effects and safety of intravitreal corticosteroid implants. Results Four eligible studies were included. Compared with the sham group, the ORs for ≥15 letter improvement of visual acuity in the high-dose and low-dose groups were 1.89 (95% CI 1.33–2.69, P=0.0004) and 1.62 (95% CI 1.10–2.41, P=0.02), respectively. The weight mean differences in central retinal thickness increases were −75.46 (95% CI −90.29, −60.63, P<0.0001) and −46.47 (95% CI −92.08, −0.86, P=0.05), respectively. However, the ORs for increased intraocular pressure in both intervention groups were higher than in the sham group, and were 11.50 (95% CI 7.24–18.28, P<0.00001) and 10.30 (95% CI 6.49–16.36, P<0.00001), respectively. The incidence of cataract was 7.25 (95% CI 5.68–9.25, P<0.00001) and 3.56 (95% CI 1.28–9.96, P=0.02) in the two intervention groups, respectively. There was no significant difference between the intervention groups except for the incidence of cataract in which the OR was 1.59 (95% CI 1.28–1.97, P<0.001). Conclusion Intravitreal corticosteroid implants are effective in treating macular edema. However, the efficacy is not related to corticosteroid dose.