A sutureless technique for securing leaking sclerotomies with viscoelastic substances in 23-gauge microincision vitrectomy surgery.

AIM: To introduce and evaluate the clinical efficacy of a new technique, the use of viscoelastic substances (VS) to close leaking sclerotomy in 23G microincision vitrectomy, and to observe its effect on the visual acuity and intraocular pressure (IOP) of patients. METHODS: Patients who underwent 23G vitrectomy in Ningbo Eye Hospital before the use of VS technique (June 2019 to September 2020) and after the use of VS technique (October 2020 to December 2021) were selected as the subjects of this study. The above cases underwent operation by the same surgeon and were retrospectively analyzed. VS technique was used as the alternative to suturing, in which a small amount of VS was injected at the leaking sclerotomy and then gently massaged to confirm leaking sclerotomy closure. RESULTS: A total of 174 eyes were covered in the study, including 84 eyes in the control group (before the use of VS technique) and 90 eyes in the VS technique group. The number of eyes that needed to be sutured decreased considerably from 42.9% in the control group to 3.3% in the VS technique group, and the proportion of subconjunctival hemorrhage at 1-2d after surgery decreased remarkably from 35.7% in the control group to 2.2% in the VS technique group. No substantial differences in the incidence of mean IOP and low IOP were found between 1-2 and 3-20d after surgery in the VS technique group. No major complications associated with VS technique were identified during the study. CONCLUSION: In 23G microincision vitrectomy, VS technique is a safe, simple, and effective method to close leaking sclerotomy.

Effects of Anti-Vascular Endothelial Growth Factor Drugs Before and After Pars Plana Vitrectomy in Patients with Polypoidal Choroidal Vasculopathy and Vitreous Hemorrhage.

Purpose: To compare the clinical effects of postoperative versus perioperative injection of anti-vascular endothelial growth factor (VEGF) drugs before and after pars plana vitrectomy (PPV) in patients with vitreous hemorrhage secondary to polypoidal choroidal vasculopathy (PCV). Methods: This was a retrospective study of patients who underwent PPV due to vitreous hemorrhage between October 2013 and June 2019 at Ningbo Eye Hospital. The patients who underwent PPV surgery due to PCV-secondary vitreous hemorrhage were included. The primary outcome was the changes in best-corrected visual acuity. The secondary outcome was the central macular thickness. Results: Compared with the postoperative group (n = 20), the perioperative group (n = 18) showed a smaller number of postoperative anti-VEGF injections (5.1 ± 0.8 vs. 8.0 ± 1.5, P < 0.05) and lower frequencies of early hyphema (5.6% vs. 30.0%, P < 0.05), and recurrent vitreous hemorrhage (11.1% vs. 30.0%, P < 0.05). The logarithm of minimal angle resolution (LogMAR) was smaller in the perioperative group compared with the postoperative group at 1 week, 1 month, and 3 months after PPV (P < 0.05), but there were no differences thereafter. Compared with the postoperative group, the perioperative group had thinner fovea at 1 week, 1 month, and 3 months (P < 0.05), but the differences disappeared after 3 months. Conclusion: In patients with PCV and vitreous hemorrhage, compared with postoperative anti-VEGF, perioperative anti-VEGF could reduce the difficulty of surgery and reduce the occurrence of postoperative complications, but there were no differences in long-term vision and macular thickness after surgery.

The P300/XBP1s/Herpud1 axis promotes macrophage M2 polarization and the development of choroidal neovascularization.

Neovascular age-related macular degeneration (AMD), which is characterized by choroidal neovascularization (CNV), leads to vision loss. M2 macrophages produce vascular endothelial growth factor (VEGF), which aggravates CNV formation. The histone acetyltransferase p300 enhances the stability of spliced X-box binding protein 1 (XBP1s) and promotes the transcriptional activity of the XBP1s target gene homocysteine inducible endoplasmic reticulum protein with ubiquitin-like domain 1 (Herpud1). Herpud1 promotes the M2 polarization of macrophages. This study aimed to explore the roles of the p300/XBP1s/Herpud1 axis in the polarization of macrophages and the pathogenesis of CNV. Hypoxia-induced p300 interacted with XBP1s to acetylate XBP1s in RAW264.7 cells. Additionally, hypoxia-induced p300 enhanced the XBP-1s-mediated unfolded protein response (UPR), alleviated the proteasome-dependent degradation of XBP1s and enhanced the transcriptional activity of XBP1s for Herpud1. The hypoxia-induced p300/XBP1s/Herpud1 axis facilitated RAW264.7 cell M2 polarization. Knockdown of the p300/XBP1s/Herpud1 axis in RAW264.7 cells inhibited the proliferation, migration and tube formation of mouse choroidal endothelial cells (MCECs). The p300/XBP1s/Herpud1 axis increased in infiltrating M2-type macrophages in mouse laser-induced CNV lesions. Blockade of the p300/XBP1s/Herpud1 axis inhibited macrophage M2 polarization and alleviated CNV lesions. Our study demonstrated that the p300/XBP1s/Herpud1 axis in infiltrating macrophages increased the M2 polarization of macrophages and the development of CNV.

Scleral Buckling with Viscoelastics or Gas Injection for Bulging Retinal Detachments: A Retrospective Cohort Study.

OBJECTIVE: To examine the use of a viscoelastic agent instead of air in the vitreous cavity during surgery for scleral buckling. METHODS: This was a retrospective cohort study of patients who underwent scleral buckling surgery for bulging rhegmatogenous retinal detachment (RRD) at Ningbo Eye Hospital from 07/2016 to 12/2019. The patients were grouped into drainage, air injection, cryotherapy and explant (DACE) and drainage, viscoelastic injection, cryotherapy, and explant (DVCE) groups, which were comparatively assessed. RESULTS: There were 25 and 22 patients in the DVCE and DACE groups, respectively. The surgery was significantly shorter with DVCE than DACE (P < 0.05), with less intraoperative external pressure adjustment (P < 0.05). BCVA was lower in the DVCE group at 1 week compared with the DACE group (P < 0.05). Successful retinal reattachment was observed in 92.0% and 81.8% of the DVCE and DACE groups, respectively (P < 0.05). Cases requiring laser replenishing after the operation were less in the DVCE group compared with the DACE group (P < 0.05). There were no differences in complications and intraocular pressure between the two groups (all P < 0.05). CONCLUSION: DVCE has better operative characteristics and faster vision recovery than DACE, with similar outcomes.

Dysfunctional Nurr1 promotes high glucose-induced Müller cell activation by up-regulating the NF-κB/NLRP3 inflammasome axis.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes mellitus (DM). During DR, high glucose levels induce Müller cell gliosis, and the dysfunction of Müller cells further promotes the pathogenesis of DR. Transcription factor nuclear receptor subfamily 4 group A member 2 (Nurr1) inhibits the inflammatory response by suppressing nuclear factor-kappa B (NF-κB) and downregulating the downstream NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome. This study aimed to investigate whether Nurr1 dysfunction in Müller cells promoted the NF-κB/NLRP3 inflammasome axis during DR. In vitro, Nurr1 expression and nuclear translocation decreased in Müller cells exposed to high glucose levels; therefore, p65 was activated, and the downstream NLRP3 inflammasome was up-regulated via the interaction of p65 with its promoter. These phenomena promoted Müller cell activation and proliferation. Moreover, in vivo, gavage of the Nurr1 agonist C-DIM12 reduced retinal ganglion cell (RGC) loss in a mouse model of streptozotocin (STZ)-induced diabetes. Together, these results showed that Nurr1 played important anti-inflammatory and neuroprotective roles in Müller cells during DR, suggesting that Nurr1 may be a potential molecular target for the treatment of DR.

HSV­TK/GCV can induce cytotoxicity of retinoblastoma cells through autophagy inhibition by activating MAPK/ERK.

Retinoblastoma is an severe ophthalmic disease and the most common type intraocular malignant tumor, particularly in infants. Currently, few drugs and therapies are available. Gene therapy has been considered to be a potential treatment to cure cancer effectively and Herpes simplex virus type 1 thymidine kinase/ganciclovir (HSV­TK/GCV) is one type of suicide gene therapy that has been extensively studied. Numerous in vitro and in vivo studied have shown that this system can kill tumor cells, including liver and lung cancer cells. GCV is used as an antiviral drug, and the thymidine kinase, HSV­TK can phosphorylate GCV to GCV­TP, a competitive inhibitor of DNA synthesis, instead of guanine­5'­triphosphate in the process of DNA synthesis. This process prevents DNA chain elongation causing cell death via apoptosis. However, the toxic effects of HSV­TK/GCV on retinoblastoma cells remain unknown, and the molecular mechanisms of its therapeutic effects have not been fully elucidated. Our results suggest that HSV­TK/GCV can significantly cause the death of retinoblastoma cell lines, HXO­RB44 and Y79. Further studies have reported that this cell death is induced by the inhibition of autophagy by activating the MAPK/ERK (mitogen­activated protein kinase/ERK) signaling pathway. The mTOR inhibitor Torin1 can partially block the toxic effects of HSV­TK/GCV on HXO­RB44 cells. The above results demonstrate that the mechanism undertaken by HSV­TK/GCV to exhibit therapeutic effects mechanism may inhibit autophagy by activating MAPK/ERK. The findings of the present study may provide novel insight for the exploration of HSV­TK/GCV in the treatment of retinoblastoma.