Comprehensive assessment of growth factors, inflammatory mediators, and cytokines in vitreous from patients with proliferative diabetic retinopathy.

AIM: To assess alterations in growth factors, inflammatory mediators, and cytokines associated with vitreous-retinal diseases in vitreous humor from patients with proliferative diabetic retinopathy (PDR), and to identify potential new treatment targets and strategies. METHODS: Control vitreous samples were collected from patients with macular hole, epiretinal membranes, or rhegmatogenous retinal detachments, and PDR samples from patients with complications of PDR, who required pars plana vitrectomy. Specimens were stored at -80°C and then investigated by Luminex multi-factor assay. Parametric and nonparametric analyses of demographic characteristics and cytokine expression levels were conducted using SPSS. RESULTS: There were no significant differences in demographic characteristics between patients with and without PDR. Expression levels of growth factors [platelet-derived growth factor (PDGF)-AA, glial cell line-derived neurotrophic factor (GDNF), and vascular endothelial growth factor A (VEGFA)], inflammatory mediators [interleukin (IL)-8, IL-11, and tumor necrosis factor-α (TNF-α)] and cytokines [chemokine C-X-C ligand (CXCL)10, interferon-γ (IFN-γ), and granulocyte macrophage-colony stimulating factor (GM-CSF)] were significantly elevated in vitreous humor from patients with PDR compared with those in the control group (all P<0.05). Further, VEGFA levels were lower in patients with PDR treated with anti-VEGF injection than those who were not (P<0.05), and there was no difference between the PDR group treated with anti-VEGF and controls (P>0.05). CONCLUSION: This proof-of-concept study demonstrates the potential for combinational therapeutic strategies to ameliorate diabetic retinopathy progression by targeting growth factors, inflammatory factors, and cytokines, in addition to VEGFA.

Quantitative analysis of retinal intermediate and deep capillary plexus in patients with retinal deep vascular complex ischemia.

AIM: To quantitatively analyze the retinal intermediate and deep capillary plexus (ICP and DCP) in patients with retinal deep vascular complex ischemia (RDVCI), using 3D projection artifacts removal (3D PAR) optical coherence tomography angiography (OCTA). METHODS: RDVCI patients and gender- and age-matched healthy controls were assessed and underwent OCTA examinations. The parafoveal vessel density (PFVD) of retinal deep vascular complex (DVC), ICP, and DCP were analyzed, and the percentage of reduction (PR) of PFVD was calculated. RESULTS: Twenty-four eyes in 22 RDVCI patients (20 in acute phase and 4 in chronic phase) and 24 eyes of 22 healthy subjects were enrolled as the control group. Significant reduction of PFVD in DVC, ICP, and DCP was observed in comparison with the controls (DVC: acute: 43.59%±6.58% vs 49.92%±5.49%, PR=12.69%; chronic: 43.50%±3.33% vs 51.20%±3.80%, PR=15.04%. ICP: acute: 40.28%±7.91% vs 46.97%±7.14%, PR=14.23%; chronic: 41.48%±2.87% vs 46.43%±3.29%, PR=10.66%. DCP: acute: 45.44%±8.27% vs 51.51%±9.97%, PR=11.79%; chronic: 37.78%±3.48% vs 51.73%±5.17%, PR=26.97%; all P<0.05). No significant PR difference was found among DVC, ICP, and DCP of RDVCI in acute phase (P=0.812), but significant difference in chronic phase (P=0.006, DVC vs DCP, ICP vs DCP). No significant difference in PR between acute and chronic phases in the DVC (P=0.735) or ICP (P=0.681) was found, but significant difference in the DCP (P=0.041). CONCLUSION: The PFVD of DVC, ICP, and DCP in RDVCI is significantly decreased in both acute and chronic phases. ICP impairment is stabilized from acute to chronic phase in RDVCI, whereas subsequent DCP impairment is uncovered and can be explained by ischemia-reperfusion damage.

Segmentation of retinal fluid based on deep learning: application of three-dimensional fully convolutional neural networks in optical coherence tomography images.

AIM: To explore a segmentation algorithm based on deep learning to achieve accurate diagnosis and treatment of patients with retinal fluid. METHODS: A two-dimensional (2D) fully convolutional network for retinal segmentation was employed. In order to solve the category imbalance in retinal optical coherence tomography (OCT) images, the network parameters and loss function based on the 2D fully convolutional network were modified. For this network, the correlations of corresponding positions among adjacent images in space are ignored. Thus, we proposed a three-dimensional (3D) fully convolutional network for segmentation in the retinal OCT images. RESULTS: The algorithm was evaluated according to segmentation accuracy, Kappa coefficient, and F1 score. For the 3D fully convolutional network proposed in this paper, the overall segmentation accuracy rate is 99.56%, Kappa coefficient is 98.47%, and F1 score of retinal fluid is 95.50%. CONCLUSION: The OCT image segmentation algorithm based on deep learning is primarily founded on the 2D convolutional network. The 3D network architecture proposed in this paper reduces the influence of category imbalance, realizes end-to-end segmentation of volume images, and achieves optimal segmentation results. The segmentation maps are practically the same as the manual annotations of doctors, and can provide doctors with more accurate diagnostic data.

A quantitative comparison of five optical coherence tomography angiography systems in clinical performance.

AIM: To compare the clinical performance of 4 spectral-domain (SD) optical coherence tomography angiography (OCTA) systems: AngioVue™, AngioPlex™, Spectralis® OCTA, AngioScan, and 1 swept-source (SS) OCTA SS OCT Angio™. METHODS: Twenty-seven undilated right eyes of 27 participants underwent OCTA examination using five different systems respectively for both 3×3 and 6×6 mm2 scan pattern (Spectralis OCTA for 3×3 mm2 scan only). Image quality, including vessel valid visibility and the number of motion artifacts, and acquisition time were evaluated. Repeated measures analysis of variance (ANOVA) with Bonferroni's post-test and Friedman test with Dunn's post-test were used to compare measurements. RESULTS: The age of the subjects was 28.19±5.55y (range, 23-49y). The spherical equivalent refraction was -2.55±1.84 D (range, 0.00 to -5.25 D). Significant difference was observed in the evaluation of vessel valid visibility (AngioVue the highest: 0.111±0.031 for 3×3 mm2 scan and 0.128±0.020 for 6×6 mm2 scan), number of motion artifacts (AngioVue the fewest: 0.778±1.086 for 3×3 mm2 scan and 0.333±0.620 for 6×6 mm2 scan) and acquisition time (AngioPlex the shortest: 8.537±1.921s for 3×3 mm2 scan and 8.298±1.741s for 6×6 mm2 scan; all P<0.001). CONCLUSION: There is poor agreement of measurements among systems. AngioVue provides images with the highest vessel valid visibility and the fewest motion artifacts. AngioPlex achieves the shortest acquisition.

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis.

AIM: To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab (IVR) versus laser therapy in treatment of diabetic macular edema (DME). METHODS: Pertinent publications were identified through comprehensive searches of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify randomized clinical trials (RCTs) comparing IVR+laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences (WMD) of change from baseline in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6, 12, or 24mo after initial treatment, and the risk ratios (RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12mo. Data regarding major ocular and nonocular adverse events (AEs) were collected and analyzed. The Review Manager 5.3.5 was used. RESULTS: Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR+laser significantly improved BCVA compared with laser at 6mo (WMD: 6.57; 95% CI: 4.37-8.77; P<0.00001), 12mo (WMD: 5.46; 95% CI: 4.35-6.58; P<0.00001), and 24mo (WMD: 3.42; 95% CI: 0.84-5.99; P=0.009) in patients with DME. IVR+laser was superior to laser in reducing CRT at 12mo from baseline with statistical significance (WMD: -63.46; 95% CI: -101.19 to -25.73; P=0.001). The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR+laser arms compared with laser (RR: 2.13; 95% CI: 1.77-2.57; P<0.00001 and RR: 0.37; 95% CI: 0.22-0.62; P=0.0002, respectively). As for AEs, the pooled results showed that a significantly higher proportion of patients suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye) in IVR+laser group compared to laser group (RR: 3.29; 95% CI: 1.53-7.09; P=0.002 and RR: 3.02; 95% CI: 1.24-7.32; P=0.01, respectively). The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR+laser and laser alone. CONCLUSION: The results of our analysis show that IVR+laser has better availability in functional (improving BCVA) and anatomic (reducing CRT) outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR+laser may get a higher risk of suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye).

[Analysis of XPS in the removal of Se(IV) from groundwater with pyrite].

Selenium (Se) is an elementary trace nutrient element for human but there is a very narrow range between deficit and toxic levels. Furthermore, excessive intake of Selenium is harmful for human. The product species of selenite which was removal by pyrite particles was studied in the present research In the experiments, the pyrite particles were prepared by the wet ball mill method, and surface analyses of pyrite before and after contact with Se(IV) were conducted using X-ray photoelectron spectroscopy (XPS). Besides, the prepared pyrite samples were also characterized using both X-ray diffraction (XRD) and scanning electron microscope (SEM). X-ray diffraction analysis indicated that the purity of the prepared pyrite particles was above 97%, and the characteristic diffraction peaks of the particles well matched with that of FeS2 crystalline. Scanning electron microscope determination showed the shape of the particles was approximate ball and the size was range from 80 to 180 nm. And thus the pyrite particles prepared by the wet ball mill method had less particle size, larger specific surface area and higher reactive ability. The batch experiments exhibited the pyrite particles were able to remove 95% of Se(IV) (20 mg x L(-1)) from water within 12 hours. And the kinetic tests indicated reaction process between pyrite and Se(IV) fits a pseudo-first order kinetic model, which gives a pseudo-first order rate constant(kobs) of 0.26 h(-1). XPS analyses were using the XPSPEAK program which has a Gaussian Lorentzian function. The results clearly displays that Se(IV) prefer to react with the surface-bound S2(2-) rather than reacted with the surface-bound Fe2+ of pyrite particles. From XPS graph, it can be seen that the binding energy of sulfur element and iron element composed of pyrite shifted to the left a little, which means expensive state of sulfur element and iron element appeared on the pyrite surface. Analysis of the oxidation state of Se on the surface of pyrite particles by X-ray photoelectron spectra showed evidence for the reduction of Se(VI) to insoluble element Se(0) species. Besides, a spot of Se(IV) was existence on the surface of pyrite particles. The calculation results displayed that zero-valent selenium was dominarnt. At that, redox reaction was the main process when removal of Se( IVN)in aqueous environment with pyrite, along with sorption reaction at the same time. The results of removal of Se(IV) in groundwater using pyrite offer important theoretical value and practical significance.

Extracts of black bean peel and pomegranate peel ameliorate oxidative stress-induced hyperglycemia in mice.

Oxidative stress has a central role in the progression of diabetes mellitus (DM), which can directly result in the injury of islet ß cells and consequent hyperglycemia. The aim of the present study was to evaluate the possible protective effects of black bean peel extract (BBPE), pomegranate peel extract (PPE) and a combination of the two (PPE + BBPE) on streptozotocin-induced DM mice. Oxidative stress was assessed by the levels of total antioxidative capability and glutathione in the serum. Fasting blood glucose and insulin levels, as well as the pancreas weight index and the histological changes in the pancreas, were also determined. The results showed that, after fours weeks of treatment with PPE, BBPE or PPE + BBPE, DM mice showed, to different degrees, a decrease in blood glucose, increases in insulin secretion and the pancreas weight index, and an increase in antioxidative activity. These changes were particularly evident in the DM mice subjected to the combined intervention strategy of PPE + BBPE. The histological findings indicated that the injury to the pancreatic islets in DM mice was also ameliorated following treatment. In conclusion, PPE and BBPE, particularly the combination of the two, have the ability to ameliorate hyperglycemia by inhibiting oxidative stress-induced pancreatic damage; this finding may be useful in the prevention and treatment of DM.