Outcomes of Eyes Lost to Follow-Up in Patients with Central Retinal Vein Occlusion Who are Receiving Anti-Vascular Endothelial Growth Factor Treatment.

BACKGROUND: To evaluate the anatomic and functional outcomes in eyes of patients with macular edema (ME) caused by central retinal vein occlusion (CRVO) who were lost to follow-up (LTFU) for more than 6 months following treatment with anti-vascular endothelial growth factor (VEGF) therapy and to determine the predictive factors of visual prognosis in these patients. METHODS: This study was conducted as a retrospective, case series investigation. Patients whose eyes were receiving intravitreal anti-VEGF treatment for CRVO-ME, with the next follow-up visit occurring more than 6 months following treatment were identified. Baseline disease characteristics (at the last visit before being LTFU), cause and duration of treatment interruption, and the resulting disease progression, complications, and outcomes were assessed. Baseline characteristics predictive of visual outcome were also analyzed. RESULTS: This study included a total of 17 eyes of 17 patients. The mean duration of being LTFU was 7.8 ± 2.1 months. On the return visit after being LTFU, 7 of 17 eyes (41.2%) developed neovascular complications. Despite treatment, 12 eyes (70.1%) lost ≥3 best-corrected visual acuity (BCVA) lines, with 2 eyes (11.8%) developing a final BCVA of hand motion or more severe. At the final visit, the mean logarithm of minimal angle of resolution (logMAR) BCVA deteriorated significantly compared to before being LTFU (P < 0.001). The increasing duration of being LTFU is associated with a deterioration of visual acuity prognosis. CONCLUSION: In CRVO-ME patients who are receiving anti-VEGF therapy, unintentional treatment interruptions can cause visually disastrous consequences, including irreversible blindness. Patients who were LTFU for a long period should be strongly warned about their poor visual prognosis.

Integrative analysis of competitive endogenous RNA network reveals the regulatory role of non-coding RNAs in high-glucose-induced human retinal endothelial cells.

BACKGROUND: Increasing evidence has suggested that non-coding RNAs (ncRNAs) play critical roles in the pathogenesis of diabetic retinopathy (DR), but their underlying mechanisms remain unclear. The purpose of this study was to determine latent key genes and to structure a competing endogenous RNA (ceRNA) regulatory network to discover the potential molecular mechanisms governing the effects of high glucose on human retinal endothelial cells (HRECs). METHODS: We obtained microarray data for long non-coding RNA (lncRNA) and mRNA of high-glucose-induced HREC samples from NCBI GEO datasets. The ceRNA network was screened using intersecting prediction results from miRcode, TargetScan, miRTarBase and miRDB. The protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and hub genes were obtained using the cytoHubba app. The ClusterProfiler package was applied for performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The expression of key RNAs was verified using the qRT-PCR method. A key ceRNA subnetwork was constructed based on the criticality of the genes and its binding sites were verified by luciferase reporter assay. The viability and apoptosis of HRECs were tested using the transfection of the miR-449c inhibitor. RESULTS: A total of 3,328 lncRNAs and 2,017 mRNAs were screened for differentially expressed (DE) profiles. The newly constructed ceRNA network was composed of 410 lncRNAs, 35 miRNAs and 122 mRNAs. The 10 hub genes were identified through the PPI network. GO and KEGG analysis revealed that DE mRNAs were mainly related to the positive regulation of the mRNA catabolic process, cell polarity, and the G1/S transition of mitotic and cell cycle signaling pathways. QRT-PCR was used to verify RNAs and the most important genes were screened out. A key ceRNA subnetwork OIP5-AS1/miR-449c/MYC was established. The binding site was verified by luciferase reporter assay. The expression levels of OIP5-AS1 and MYC increased after miR-449c inhibitor transfection, miR-449c decreased, HRECs activity increased, and apoptosis decreased, compared with the control group. CONCLUSION: We successfully built the key ceRNA subnetwork, OIP5-AS1/miR-449c/MYC, by applying the GEO database for data analysis and mining. The results from the ceRNA network allow us to better understand the effect of ncRNAs on HRECs under hyperglycemic conditions and the pathogenesis of DR.

HMGB1 upregulates NF-kB by inhibiting IKB-α and associates with diabetic retinopathy.

AIMS: Diabetic retinopathy (DR) is the main cause of blindness in adults and investigating new therapeutic targets for DR is necessary. This study aimed to investigate the effect of high-mobility group box 1 (HMGB1) protein and its mechanism in diabetic retinopathy (DR) were investigated. MAIN METHODS: Human retinal endothelial cells (HREC) were uesd for chip-seq. Sprague Dawley (SD) rats were randomly divided into control group, HMGB1 group, diabetes mellitus (DM) combined with HMGB1 siRNA group, and DM group. Next, eyeballs were removed and retinas were detached for western blot. The DM model of cell was built by increasing the glucose concentration in cell culture medium. The regulation of HMGB1 was achieved by short hairpin (sh)-HMGB1 transfection, then, the transfected cells were harvested for luciferase assay, western blot and qRT-PCR analyses as well as proliferation and apoptosis detection. KEY FINDINGS: Chip-seq and luciferase assay showed the possible transcription factor functions of HMGB1 and IKB-α was one of the HMGB1 binding sites. In vivo and in vitro results indicated high expression of HMGB1 and NF-kB and low expression of IKB-α in DR and the expression of IKB-α and NF-kB was regulated by HMGB1. Moreover, cell assays showed that HMGB1 inhibited cell proliferation and promoted apoptosis. SIGNIFICANCE: The results from the present study showed that HMGB1 may be involved in the pathogenesis of DR as a transcription factor through NF-kB pathway. Therefore, blockade of HMGB1 may be a new method for the treatment of DR.

Serum microRNA-221 as a biomarker for diabetic retinopathy in patients associated with type 2 diabetes.

AIM: To investigate the candidate microRNA (miRNA), miR-221 as a novel biomarker for diabetic retinopathy (DR) in patients associated with type 2 diabetes (T2D). METHODS: The subjects involved were divided into four groups: healthy control (HC), no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) group. Serum miR-221 was validated by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Also, serum angiotensin II (Ang II) and vascular endothelial growth factor (VEGF) were examined by enzyme-linked immunosorbent assay. In addition, receiver operating characteristic (ROC) curve was performed to explore the diagnostic accuracy of miR-221, Ang II and VEGF for DR in patients with T2D. Spearman's rank correlation coefficient was executed to estimate the correlations of serum miR-221 with metabolic parameters and serum markers in patients with T2D. RESULTS: Primarily, serum miR-221, Ang II and VEGF were increased significantly in T2D patients compared to HC participant respectively, and progressive up-regulated in NDR, NPDR and PDR groups (P<0.001). Additionally, miR-221 in serum was remarkably positively correlated with metabolic parameters such as glycated hemoglobin (r=0.310, P=0.002) and homeostasis model assessment for insulin resistance (r=0.413, P<0.001), as well as serum markers for instance Ang II (r=0.667, P<0.001) and VEGF (r=0.499, P<0.001). Furthermore, serum miR-221 (AUC, 0.894; 95%CI, 0.833-0.955; P<0.001), Ang II (AUC, 0.888; 95%CI, 0.828-0.949; P<0.001) and VEGF (AUC, 0.785; 95%CI, 0.695-0.875; P<0.001) had evidently diagnostic efficiency in DR, and miR-221 is the most effective among them. CONCLUSION: Serum miR-221 as a potential biomarker could be related to not only occurrence but also progression for DR in patients with T2D. However, a prospective clinical trial is warranted.

Serum microRNA-211 as a biomarker for diabetic retinopathy via modulating Sirtuin 1.

Diabetic retinopathy (DR) is a progressive microvascular complication associated with diabetes, and remains the leading cause of preventable blindness worldwide. Recent studies have revealed that microRNAs (miRNAs) were involving in the physiological and pathophysiological processes of diabetes and its microvascular and macrovascular complications. The purpose of the current investigation is to identify the candidate miR-211 as a novel biomarker for occurrence and progression of DR in clinical study and experimental research. Firstly, miR-211 was considered as a candidate miRNA identifying by miRNA microarray analysis, Venn diagram analysis, real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and receiver operating characteristic curve in clinical study. Then, the predicted Sirtuin 1 (SIRT1) may be the target gene of miR-211 searching by TargetScan 7.2. Moreover, miR-211 was significantly up-regulated, while SIRT1 mRNA significantly down-regulated measuring by qRT-PCR, meanwhile, SIRT1 protein was significantly down-regulated in coincidence with SIRT1 mRNA detecting by western blot, and even aggravated associated with diabetes duration in diabetic retinal tissues of vivo experiment. Additionally, miR-211 was directly targeted SIRT1 confirming by dual-luciferase reporter assay. Furthermore, with transfection of antagomiR-211, the apoptosis of HUVECs was significantly suppressed employing by flow cytometry analysis, nevertheless the viability of HUVECs was significantly promoted exploiting by Cell Counting Kit-8 assay. Finally, SIRT1 mRNA and SIRT1 protein were significantly up-regulated testing by qRT-PCR and western blot respectively in hyperglycemic HUVECs transfected with antagomiR-211 of vitro experiment. Consequently, the current clinical study and experimental research imply that serum miR-211 as a novel biomarker with high sensitivity and specificity could be associated with occurrence and progression of DR via targeting SIRT1.

Three-year results of small incision lenticule extraction and wavefront-guided femtosecond laser-assisted laser in situ keratomileusis for correction of high myopia and myopic astigmatism.

AIM: To compare and calculate the 3-year refractive results, higher-order aberrations (HOAs), contrast sensitivity (CS) and dry eye parameters after small incision lenticule extraction (SMILE) and wavefront-guided femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for correction of high myopia and myopic astigmatism. METHODS: In this prospective, non-randomized comparative study, 78 eyes with spherical equivalent (SE) of -8.11±1.09 diopters (D) received a SMILE surgery, and 65 eyes with SE of -8.05±1.12 D received a wavefront-guided FS-LASIK surgery with the VisuMax femtosecond laser (Carl Zeiss Meditec, Jena, Germany) for flap cutting. Visual acuity, manifest refraction, CS, HOAs, ocular surface disease index (OSDI) and tear break-up time (TBUT) were evaluated during a 3-year follow-up. RESULTS: The difference of uncorrected distance visual acuity (UDVA) postoperatively was achieved at 1mo and at 3mo, whereas the difference of the mean UDVA between two groups at 3y were not statistically significant (t=-1.59, P=0.13). The postoperative change of SE was 0.89 D in the FS-LASIK group (t=5.76, P=0.00), and 0.14 D in the SMILE group (t=0.54, P=0.59) from 1mo to 3y after surgery. At 3-year postoperatively, both HOAs and spherical aberrations in the SMILE group were obviously less than those in the FS-LASIK group (P=0.00), but the coma root mean square (RMS) was higher in the SMILE group (0.59±0.26) than in the FS-LASIK group (0.29±0.14, P=0.00). The mesopic CS values between two groups were not statistically significant at 3y postoperatively. Compared with the FS-LASIK group, lower OSDI scores and longer TBUT values were found in the SMILE group at 1mo and 3mo postoperatively. With regard to safety, no eye lost any line of CDVA in both groups at 3y after surgery. CONCLUSION: Both SMILE and wavefront-guided FS-LASIK procedures provide good visual outcomes. Both procedures are effective and safe, but SMILE surgery achieve more stable long-term refractive outcome and better control of early postoperative dry eye as compared to FS-LASIK.

Raman spectroscopy of graphene-based materials and its applications in related devices.

Graphene-based materials exhibit remarkable electronic, optical, and mechanical properties, which has resulted in both high scientific interest and huge potential for a variety of applications. Furthermore, the family of graphene-based materials is growing because of developments in preparation methods. Raman spectroscopy is a versatile tool to identify and characterize the chemical and physical properties of these materials, both at the laboratory and mass-production scale. This technique is so important that most of the papers published concerning these materials contain at least one Raman spectrum. Thus, here, we systematically review the developments in Raman spectroscopy of graphene-based materials from both fundamental research and practical (i.e., device applications) perspectives. We describe the essential Raman scattering processes of the entire first- and second-order modes in intrinsic graphene. Furthermore, the shear, layer-breathing, G and 2D modes of multilayer graphene with different stacking orders are discussed. Techniques to determine the number of graphene layers, to probe resonance Raman spectra of monolayer and multilayer graphenes and to obtain Raman images of graphene-based materials are also presented. The extensive capabilities of Raman spectroscopy for the investigation of the fundamental properties of graphene under external perturbations are described, which have also been extended to other graphene-based materials, such as graphene quantum dots, carbon dots, graphene oxide, nanoribbons, chemical vapor deposition-grown and SiC epitaxially grown graphene flakes, composites, and graphene-based van der Waals heterostructures. These fundamental properties have been used to probe the states, effects, and mechanisms of graphene materials present in the related heterostructures and devices. We hope that this review will be beneficial in all the aspects of graphene investigations, from basic research to material synthesis and device applications.

Filter-based ultralow-frequency Raman measurement down to 2 cm-1 for fast Brillouin spectroscopy measurement.

Simultaneous Stokes and anti-Stokes ultralow-frequency (ULF) Raman measurement down to ∼2 cm-1 or 60 GHz is realized by a single-stage spectrometer in combination with volume-Bragg-grating-based notch filters. This system reveals its excellent performance by probing Brillouin signal of acoustic phonons in silicon, germanium, gallium arsenide, and gallium nitride. The deduced sound velocity and elastic constants are in good accordance with previous results determined by various methods. This system can shorten the integration time of the Brillouin signal with a good signal-to-noise ratio by more than 2000-fold compared to a Fabry-Perot interferometer (FPI). This study shows how a filter-based ULF Raman system can be used to reliably achieve Brillouin spectroscopy for condensed materials with high sensitivity and high signal-to-noise ratio, stimulating fast Brillouin spectrum measurements to probe acoustic phonons in semiconductors.

Association of MTHFR C677T with total homocysteine plasma levels and susceptibility to Parkinson's disease: a meta-analysis.

The C677T single-nucleotide polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR) may elevate homocysteine (Hcy) levels and increase the risk of Parkinson's disease (PD); however, results are conflicting. Our aim was to resolve contradictions in the literature and to determine whether MTHFR C677T has a significant role in regulating Hcy levels and/or is a significant risk factor for PD. MEDLINE, EMBASE, the Cochrane Library, China Biological Medicine Database and Google Scholar were searched until May 2014. Strict selection and exclusion criteria were determined, and odds ratios (ORs)/weighted mean differences (WMDs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed using STATA 12.0. Fifteen studies that together assessed 2690 PD cases and 8465 controls were included. Meta-analysis showed that no significant difference in the distribution of MTHFR C677T between PD cases and controls was found. While stratifying for ethnicity, significant association was revealed in Europeans (T vs. C, OR = 1.17, 95 % CIs 1.04-1.31) but not in Asians. Significant association between the T allele and increased Hcy levels was found in PD cases and controls; Hcy levels were higher in PD cases and controls carrying the MTHFR T677 allele than in non-carriers (TT vs. CC, PD WMD = 6.50, 95 % CIs 6.20-6.80; controls WMD = 4.52, 95 % CIs 4.24-4.80). Other within-group comparisons showed similar results. This meta-analysis suggests that MTHFR C667T may confer PD susceptibility in Europeans. The T allele may be an independent risk factor for elevated Hcy levels in PD patients.

Meta-analysis of the relationship between homocysteine, vitamin B12, folate, and multiple sclerosis.

A meta-analysis was conducted to assess the relationship between serum homocysteine, vitamin B(12), and folate levels in patients with multiple sclerosis (MS). The DerSimonian and Laird Q test was used to evaluate the degree of heterogeneity between studies and a funnel plot was used to assess publication bias. The pooled effect size (standardized mean difference [SMD]) between patients with MS and control patients) from a random effects model was 0.84 (95% confidence interval: 0.18, 1.49) for homocysteine and -0.25 (-0.45, -0.04) for vitamin B(12), and from a fixed effects model was 0.98 (0.80, 1.16) for homocysteine and -0.25 (-0.41, -0.09) for vitamin B(12). Both nutrients were statistically significant, but the SMD for folate was not. Patients with MS were found to have raised homocysteine levels but low B(12) levels, which might contribute to the pathogenesis of MS.

Efficacy and tolerability of one-site versus two-site phaco-trabeculectomy: a meta-analysis of randomized controlled clinical trials.

BACKGROUND: Phacotrabeculectomy can be performed using one-site or two-site incisions. This meta-analysis evaluated the efficacy and tolerability of one-site versus two-site phacotrabeculectomy in the treatment of patients with coexisting cataract and glaucoma. METHODS: A comprehensive literature search was performed according to the Cochrane Collaboration methodology to identify randomized controlled clinical trials comparing one-site with two-site phacotrabeculectomy. Studies meeting our predefined criteria were included in the meta-analysis. Efficacy estimates were measured by weighted mean difference (WMD) for the percentage intraocular pressure (IOP) reduction from baseline to end point, relative risk (RR) for the proportion of patients with a best-corrected visual acuity (BCVA) of 0.5 or better after surgery and complete success rates. Tolerability estimates were measured by RR for adverse events. All of outcomes were reported with 95% confidence interval (95%CI). Data were synthesised by Stata 10.1 for Windows. RESULTS: Two-site phacotrabeculectomy was associated with greater reductions in IOP than the one-site procedure (WMD: -5.99, 95%CI: -10.74 - -1.24, P = 0.01). A greater proportion of patients also achieved a BCVA of 0.5 or better (RR: 0.91, 95%CI: 0.74 - 1.12, P = 0.36) and the target IOP without anti-glaucoma medication at the study end point (RR: 0.94, 95%CI: 0.83 - 1.07, P = 0.34) after two-site than one-site phacotrabeculectomy, but the differences were not significant. There were no significant differences in adverse events between two surgical procedures. CONCLUSIONS: Two-site phacotrabeculectomy is superior to one-site phacotrabeculectomy in reducing IOP, but other post-operative effects are similar. One-site and two-site phacotrabeculectomies have similar adverse event rates.

Efficacy and tolerability of one-site versus two-site phacotrabeculectomy: a meta-analysis.

AIM: To evaluate the efficacy and tolerability of one-site versus two-site phacotrabeculectomy in the treatment of patients with coexisting cataract and glaucoma. METHODS: A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify controlled clinical trials comparing one-site with two-site phacotrabeculectomy. The studies meeting the predefined criteria were reviewed systematically by meta-analysis. Efficacy estimates were measured by standardised mean difference (SMD) for the percentage intraocular pressure (IOP) reduction from baseline to end point, odds ratio (OR) for the percentage having a best-corrected visual acuity (BCVA) of 0.5 or better after surgery and relative risk (RR) for complete success rates. Tolerability estimates were measured by RR for adverse events. All of outcomes were reported with 95% confidence interval (CI). Data were synthesised by Stata 10.1 for Windows. RESULTS: Two-site phacotrabeculectomy was associated with numerically greater, and significant efficacy than one-site in lowering IOP (SMD, -0.19; 95% CI, -0.33 to -0.04; P=0.01). Numerically greater, but nonsignificant proportions of two-site patients than one-site patients had a BCVA of 0.5 or better (OR, 0.65; 95% CI, 0.30 to 1.39; P=0.26).Numerically greater, but nonsignificant proportions of two-site patients than one-site patients achieved the target IOP without anti-glaucoma medication at the end point (RR, 0.94; 95% CI, 0.84 to 1.04; P=0.22). Furthermore, there was nonsignificant difference in adverse events between two surgical procedures. CONCLUSION: The efficacy of two-site phacotrabeculectomy appears to be superior to one-site phacotrabeculectomy. One-site and two-site phacotrabeculectomy are similarly tolerable in postoperative adverse events.

[Meta-analysis on relationship between hyperhomocysteinemia and multiple sclerosis].

OBJECTIVE: To determine the relationship between hyperhomocysteinemia and multiple sclerosis (MS). METHODS: Cochrane, Medline, EMbase, Springerlink, Highwire, CBM, CNKI and some other databases were searched for literatures. Articles were identified using the Medical Subject Heading term "hyperhomocysteinemia, homocysteine, multiple sclerosis". The methodological quality of internalized literatures were evaluated, screened and heterogeneity tested. Case control studies involving unrelated subjects and valid data were extracted and analyzed in Stata 8.0. RESULTS: Nine studies were included in this review. The involved 1146 subjects were made of 676 patients and 470 controls. A meta-analysis showed that the level of homocysteine in MS was higher than that in controls (standardized mean difference 1.25, 95%CI: 0.48 - 2.01). The analytical result of sensitivity proved that the result of meta-analysis was coherent. CONCLUSION: Hyperhomocysteinemia is associated with MS, and it may contribute to the pathological course of MS.