A Multicenter Prospective Randomized Controlled Study of a New Corneal Wetting Agent During Ophthalmologic Surgery.

INTRODUCTION: A multicenter prospective randomized controlled study was used to investigate the effect and safety of a new corneal wetting agent called the Corneal Surface Viscoelastic Protector (CsVisc, Success Bio-Tech Co., Ltd, China), on the corneal epithelium during ophthalmic surgery by comparison with the commercially available Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). METHODS: This multicenter prospective randomized controlled study comprised patients scheduled for cataract surgery and pars plana vitrectomy. The patients were randomly assigned to receive either a new corneal wetting agent (CsVisc) or Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). Optical clarity during surgery, application frequency, duration of effect, diffusion time of corneal wetting agents, fluorescein staining, intraocular pressure (IOP), tear-film break-up time (TBUT), and Schirmer I test (SIT) were assessed. Adverse events were noted on the designated patient case report forms. RESULTS: A total of 149 eyes (149 patients, mean age 62 years; range 25-80 years) were included in the study. There were 74 eyes in the control group and 75 eyes in the study group. In patients who underwent vitrectomy, the frequency of application was 1.62 ± 1.03 in the study group and 1.39 ± 0.66 in the control group, with no significant difference (P = 0.399), and the duration of effect was 19.16 ± 6.94 min in the study group and 19.06 ± 7.22 min in the control group, with no significant difference (P = 0.835). The optical clarity of the study group was not significantly different from that of the control group (P = 0.485). In patients who underwent cataract surgery, the frequency of application was 1.10 ± 0.38 in the study group and 1.07 ± 0.26 in the control group, and the difference was not significant (P = 0.950). The difference between the duration of effect in the study group (8.32 ± 2.50 min) and the control group (7.63 ± 2.52 min) was not significant (P = 0.310). The difference in optical clarity scores between the two groups was not statistically significant (P = 0.600). Among all patients in this study, the diffusion time of the corneal wetting agent was 14.97 ± 10.07 s in the control group and 11.23 ± 8.41 s in the study group, with a statistically significant difference (p = 0.008). The frequency of adverse events was 20.00% (15/75) in the study group and 14.86% (11/74) in the control group, with no statistically significant difference (P = 0.409). There were no serious adverse events related to the test medical device or causing patients to withdraw from the study. CONCLUSIONS: The CsVisc is safe and effective in preventing intraoperative corneal epithelial damage due to corneal dryness and can be comparable to the CP. In addition, the CsVisc has a shorter diffusion time.

Delineation of the bacterial composition in exogenous endophthalmitis using 16S rDNA sequencing.

PURPOSE: To determine the bacterial spectrum of exogenous endophthalmitis of different origins, namely, posttraumatic, postcataract surgery, filtering bleb-associated, and intravitreal treatment-related endophthalmitis, using the 16S rDNA sequencing method. METHODS: Aqueous humor or vitreous humor samples were collected from 24 endophthalmitis patients. Traditional cultivation and 16S rDNA sequencing were conducted with these samples. Three senile cataract controls and one intraocular irrigating solution were used as sequencing control. RESULTS: Eleven of the 24 samples (45.8%) obtained positive bacterial cultivation, and each sample positive for only one species. The 11 culture-positive species could all be identified in their corresponding sequencing results, but only four strains being the top one pathogen in the sequencing. A total of 567 species were isolated using 16S rDNA sequencing, with the top five species being Pseudomonas sp., Staphylococcus epidermidis, Staphylococcus sp., Streptococcus sp., and Enterococcus faecalis. The dominant bacterial strains varied among the different endophthalmitis categories but with no significant difference in the overall bacterial spectrum. Bacterial atlas containing Pseudomonas, Streptococcus, Staphylococcus, Actinomycetales_unclassified, Thermus, and Janibacter was shared by the four categories. Aqueous humor bacterial profile showed a higher overlap with contaminating bacteria from the environment. CONCLUSIONS: 16S rDNA sequencing is more efficient for endophthalmitis pathogen screening than the traditional cultivation method in terms of positive detection rate and the number of bacteria identified. But the risk of environmental contamination exists when using 16S rDNA sequencing method for endophthalmitis diagnosis. Different categories of endophthalmitis displayed diversified bacterial composition.

Bruton's Tyrosine Kinase (BTK) Inhibitor RN486 Overcomes ABCB1-Mediated Multidrug Resistance in Cancer Cells.

Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) remains one of the most vital factors leading to multidrug resistance (MDR). It is important to enhance the effect and bioavailability of chemotherapeutic drugs that are substrates of ABCB1 transporter in ABCB1-overexpression cancer cells and reverse ABCB1-mediated MDR. Previous, we uncovered that the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is a potent reversal agent to overcomes paclitaxel resistance in ABCB1-overexpressing cells and tumors. In this study, we explored whether RN486, another BTK inhibitor, was competent to surmount ABCB1-mediated MDR and promote relevant cancer chemotherapy. We found that RN486 significantly increased the efficacy of paclitaxel and doxorubicin in both drug-selected carcinoma cells and transfected cells overexpressing ABCB1. Mechanistic studies indicated that RN486 dramatically attenuated the drug efflux activity of ABCB1 transporter without altering its expression level or subcellular localization. The ATPase activity of ABCB1 transporter was not affected by low concentrations but stimulated by high concentrations of RN486. Moreover, an interaction between RN486 with ABCB1 substrate-binding and inhibitor binding sites was verified by in silico docking simulation. The results from our study suggest that RN486 could be a reversal agent and could be used in the novel combination therapy with other antineoplastic drugs to conquer MDR-mediated by ABCB1 transporter in clinics.

Intraoperative Cefuroxime Irrigation Prophylaxis for Acute-Onset Endophthalmitis After Phacoemulsification Surgery.

PURPOSE: Acute-onset postoperative endophthalmitis usually compromises the visual function and anatomical integrity of the eye. The aim of this study was to evaluate the efficacy of intraoperative cefuroxime use in irrigating solution on prevention of acute-onset endophthalmitis after phacoemulsification. METHODS: This retrospective, comparative, interventional cohort study included patients who underwent phacoemulsification between January 1, 2012, and December 31, 2019. Under a uniform perioperative protocol, the patients who had surgery from January 1, 2012, to December 31, 2014, received irrigating infusion fluid containing balanced salt solution (BSS) only (group 1), and those from January 1, 2015, to December 31, 2019, received BSS with cefuroxime (1500 µg/mL) during surgery (group 2). All eyes were evaluated postoperatively, and the eyes suspected to have endophthalmitis were assessed and treated by a consultation team. The rates of postoperative endophthalmitis in these two groups were calculated. RESULTS: A total of 61,299 eyes were included over the eight years. Among these eyes, 11 in group 1 (0.07% of 15,948 eyes) and 5 in group 2 (0.01% of 45,351 eyes) developed endophthalmitis, and the difference was significant (P < 0.01). Five among 16 patients (31.25%) with endophthalmitis were positive in bacterial culture. The positive rate of bacterial culture was not significantly different between group 1 (4/11) and group 2 (1/5) (P > 0.05). No adverse events related to the irrigation of cefuroxime were found. CONCLUSION: Intraoperative cefuroxime irrigation (1500 µg/mL) could decrease the rate of postoperative endophthalmitis after phacoemulsification by 7-fold. This study provides evidence that intraoperative irrigation with cefuroxime is effective as an antibiotic prophylaxis for endophthalmitis.

Corneal Denervation Causes Epithelial Apoptosis Through Inhibiting NAD+ Biosynthesis.

Purpose: To determine if trigeminal innervations of the corneal epithelium maintains its integrity and homeostasis through controlling the nicotinamide adenine dinucleotide (NAD) content of this tissue. Methods: Corneal denervation of C57BL/6 mice was induced by squeezing the nerve bundles that derive from the trigeminal ganglion and was confirmed by whole-mount corneal nerve staining and the sensation test. The apoptosis of the corneal epithelium was examined by TUNEL assay and annexin V/propidium iodide staining. NAD biosynthesis-related enzymes were analyzed by quantitative PCR, immunofluorescence staining, and Western blotting. FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), exogenous nicotinamide mononucleotide (NMN), and NAD+ were used to evaluate the effect of NAD+ on the apoptosis of cultured corneal epithelial cells and epithelial detachment in denervated mice. Protein expression that related to apoptosis and phosphorylation were analyzed by Western blotting. Results: The denervated mice showed spontaneous corneal epithelial detachment and cell apoptosis accompanied with impaired epithelial NAD+ contents due to low levels of NAMPT. Similarly, inhibition of NAMPT recapitulated epithelial detachment as in denervated mice and induced apoptosis in cultured corneal epithelial cells. The replenishment of NMN or NAD+ partially slowed down corneal nerve fiber degeneration, reduced the epithelial defect in denervated mice, and improved apoptosis induction in FK866-treated cells by restoring the activation levels of SIRT1, AKT, and CREB. Conclusions: Corneal denervation lowered epithelial NAD+ contents through reducing the expression of NAMPT and caused cell apoptosis and epithelial defects, suggesting that corneal innervations contribute to epithelial homeostasis by regulating NAD+ biosynthesis.

Complement 5b-9 complex-induced alterations in human RPE cell physiology.

BACKGROUND: Recent evidence shows that complements are closely related to the occurrence of choroidal neovascularization (CNV). We studied the effect of complement 5b-9 complex (C5b-9) on membrane permeability and molecular biological behavior in cultured human retinal pigment epithelium (RPE) cells and considered the role of C5b-9 in CNV. MATERIAL/METHODS: Human RPE cells were exposed to different concentrations of C5b-9 for 24 hours, then observed through light and electron microscopy. The dynamics of calcium ion change in cells exposed to sublysis C5b-9 were analyzed by confocal laser scanning microscope, and the amount of VEGF and TGF-beta2 mRNA was determined by reverse transcription polymerase chain reaction (RT-PCR) RESULTS: RPE cells were destroyed when exposed to 80 microg/ml and 40 microg/ml C5b-9. The structure of RPE cells was not obviously changed when exposed to 20 microg/ml or less C5b-9; however, pigment granules are released from the cell membrane when observed using electron microscopy. In most of the cells, calcium fluorescence intensity increased rapidly after the deposition of C5b-9, to a peak at 4 min, lasted for about 6 min, and then began to decrease. The expression of VEGF and TGF- beta2 mRNA in RPE cells with C5b-9 was increased at 4 h and decreased at 24 h, but they were higher than in the control group. CONCLUSIONS: These observations suggest C5b-9 can induce a change in membrane permeability, an increase in cytoplasmic calcium ion concentration, and significant up-regulation of angiogenic factors in cultured RPE cells, which may be one of many potential mechanisms of CNV formation.