MG132, Attenuates the Retinal Vascular Injury Through the Upregulation of Nrf2 Expression.

Purpose: This study clarifies the beneficial effects of MG132, a proteasomal inhibitor, on retinal vascular injury mediated by diabetes-induced oxidative stress through nuclear factor erythroid 2-related factor 2 (Nrf2). Methods: Diabetic rats and control animals were randomly assigned to receive MG132 or vehicle for 24 weeks, and human retinal endothelial cells (HRECs) were incubated with normal or high glucose with or without MG132. 26S proteasome activity in the rat retinas or cultured HRECs was measured using Suc-LLVY-7-amido-4-methylcoumarin. NADPH-quinone oxidoreduc-tase (NQO1), heme oxygenase (HO)-1, kelch-like ECH-associated protein 1 (Keap1) and Nrf2 were examined by Western blotting and real-time reverse transcription polymerase chain reaction. Cell apoptosis is measured through flow cytometry assay, mitochondrial reactive oxygen species (ROS) production, and retinal vascular leakage were assayed using CM-H2DCFDA fluorescent probes and Evans blue, respectively. Results: MG132 significantly inhibited the activation of 26S proteasome induced by diabetes or elevated glucose, and subsequently increased the expression of Nrf2, NQO1, and HO-1, and further reduced ROS accumulation. These changes were associated with a decrease of diabetes-induced retinal vascular leakage and retinal capillary cell apoptosis. Conclusions: MG132 decreases diabetes-induced 26S proteasome activation and exerts protective effects against retinal microvascular dysfunction in diabetic rats in association with the alleviation of retinal oxidative stress mediated by Nrf2.

Efficacy and safety of single-dose intravitreal dexamethasone implant in non-infectious uveitic macular edema: A systematic review and meta-analysis.

Purpose: We conducted a systematic review and meta-analysis to investigate the efficacy and safety of single-dose intravitreal dexamethasone (DEX) implant for treating non-infectious uveitic macular edema (UME). Methods: Studies including clinical outcomes of the DEX implant in UME were comprehensively searched in PubMed, Embase, and Cochrane databases for potential studies from inception to July 2022. The primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT) during the follow-up period. Stata 12.0 was used to perform the statistical analyses. Results: Six retrospective studies and one prospective investigation involving 201 eyes were ultimately included. Significantly improved BCVA was observed from baseline to 1 month (WMD = -0.15, 95%CI = -0.24, -0.06), 3 months (WMD = -0.22, 95%CI = -0.29, -0.15), and 6 months (WMD = -0.24, 95%CI = -0.35, -0.13), after single-dose DEX implant. When considering CMT, macular thickness of 1 month (WMD = -179.77, 95%CI = -223.45, -136.09), 3 months (WMD = -179.13, 95%CI = -232.63, -125.63), and 6 months (WMD = -140.25, 95%CI = -227.61, -52.88) decreased in comparison with baseline, with statistical significance. Conclusion: Based on the current results, this meta-analysis confirmed favorable visual prognosis and anatomical improvement in patients with UME, after receiving the single-dose DEX implant. The most common adverse event is increased intraocular pressure, which could be controlled with topical medications.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022325969.

Retinal and choroidal microvascular alterations in Behcet's disease without ocular manifestations: A systematic review and meta-analysis.

Purpose: We performed a systematic review and meta-analysis to examine the microvascular alterations in non-ocular Behcet's disease (BD) using optical coherence tomography angiography (OCTA). Methods: A comprehensive search was performed in Pubmed, Embase and Cochrane databases for eligible studies from inception to February 2022. Detailed clinical demographics were extracted from each study by two independent reviewers. The weighted mean difference (WMD) and 95% confidence intervals (CI) were used to compare the OCTA parameters between non-ocular BD and healthy controls. Stata 12.0 was adopted to conduct statistical analyses. Results: Ten cross-sectional studies involving 386 eyes in non-ocular BD and 418 eyes in healthy volunteers were ultimately included in the present analysis. When considering superficial capillary plexus (SCP) and deep capillary plexus (DCP), no significant differences of vessel densities in the whole enface image, fovea and perifovea were evaluated between two groups. Significantly reduced parafoveal vessel density of SCP was observed in non-ocular BD in comparison with healthy group (WMD = -1.33, 95%CI: -1.78, -0.89; I 2 = 0.6%), while slightly decreased parafoveal vessel density was assessed in DCP (WMD = -1.47, 95%CI: -3.30, 0.35; I 2 = 89.3%). Significantly increasing foveal avascular zone (FAZ) area was observed in non-ocular BD when compared to healthy controls (WMD = 0.11, 95%CI: 0.03, 0.19; I 2 = 95.3%). There was no significant difference in flow area of choriocapillaris between non-ocular BD and control group (WMD = 0.06, 95%CI: -0.19, 0.32; I 2 = 0%). Conclusion: Based on current analysis, our results demonstrated significantly lower parafoveal vessel density of SCP and lager FAZ area in full vasculature in non-ocular BD. The retinal microvascular alterations appear before the emergence of ocular manifestations. Systematic Trial Registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021244856].

Efficacy of prophylactic laser retinopexy in acute retinal necrosis: A systematic review and meta-analysis.

PURPOSE: We performed a systematic review and meta-analysis to assess the role of prophylactic laser retinopexy in preventing rhegmatogenous retinal detachment (RRD) in acute retinal necrosis (ARN). METHODS: Pubmed, Embase and Cochrane databases were searched for eligible studies from inception to July 2020. Comprehensive clinical demographics were extracted from each study by two independent investigators. A random effects model was selected to analyze the OR of RRD risk and visual outcome with 95%CI. Subsequent subgroup and sensitivity analysis were conducted to evaluate the source of heterogeneity. RESULTS: A total of eight studies and 247 eyes (111 prophylactic laser retinopexy eyes and 136 eyes receiving antiviral treatment) were included in this analysis. There was moderate statistical heterogeneity across all studies. When compared with routine antiviral treatment alone, RRD risk decreased in patients receiving prophylactic laser retinopexy, however, this was not statistically significant (P = 0.09, OR = 0.42, 95%CI: 0.15-1.15). There was significant improvement in BCVA during the follow-up period in the prophylactic laser retinopexy subgroup (P = 0.01, WMD = - 0.98, 95%CI: - 1.74, - 0.22). CONCLUSION: Based on current analysis, our results did not support convincing evidence of prophylactic laser in preventing RRD. Future studies featuring high-quality, multicenter trials will be required to correct baseline characteristics. TRIAL REGISTRATION: This meta-analysis has been retrospectively registered in Prospero (registration number: CRD42020201008).

Role of Prophylactic Vitrectomy in Acute Retinal Necrosis in Preventing Rhegmatogenous Retinal Detachment: Systematic Review and Meta-analysis.

PURPOSE: To evaluate the effects of prophylactic vitrectomy for rhegmatogenous retinal detachment (RRD) risk and visual outcome in acute retinal necrosis (ARN). METHODS: A systematic search of online databases was performed for articles published between 1994 June and 2020 March. The main outcomes that were assessed by a fixed effects model were RRD risk and visual outcome during a follow up period. RESULTS: A total of 7 trials involving 265 eyes (121 prophylactic vitrectomy eyes vs 144 routine antiviral treatment eyes) were analyzed in this study. RRD risk significantly decreased in the prophylactic vitrectomy group compared to the routine antiviral treatment group (P < .001, OR = 0.27, 95% CI: 0.16-0.46, I2 = 35.3%). Significantly deteriorated visual outcome was observed in the prophylactic vitrectomy group in comparison with the routine antiviral treatment group (P < .001, WMD = 0.47, 95%CI: 0.26-0.67, I2 = 32.2%). CONCLUSION: This meta-analysis of retrospective cohort studies revealed that prophylactic vitrectomy could reduce the risk of RRD. The silicone oil tamponade and long-term complications may result in deteriorated visual outcome.

Evaluation of microvasculature alterations in convalescent Vogt-Koyanagi-Harada disease using optical coherence tomography angiography.

PURPOSE: To evaluate the microvasculature alterations in convalescent Vogt-Koyanagi-Harada (VKH) disease using optical coherence tomography angiography (OCTA), and to explore the association between microvasculature and the presence of sunset glow fundus (SGF). METHODS: A cross-sectional study was conducted with 28 VKH patients at convalescent stage and 25 healthy individuals. Both eyes of each participant were enrolled. The VKH patients were classified into two subgroups based on the existence of SGF. OCTA images (3 × 3 mm) were assessed for the data of superficial capillaris plexus (SCP), deep capillaris plexus (DCP), choriocapillaris, and foveal avascular zone (FAZ). RESULTS: Compared with healthy control eyes and eyes without SGF, the vessel densities of the SCP and DCP decreased significantly in most regions of eyes with SGF (p < 0.0167). No significant difference of vascular perfusion was found between eyes without SGF and control eyes (p > 0.05). VKH patients with SGF had slightly increased FAZ area (p = 0.067) and decreased choroid flow area (p = 0.427) than those in the control group. CONCLUSION: Convalescent VKH patients with SGF showed decreased macular capillary perfusion. OCTA could serve as a sensitive tool to assess the microvasculature alterations of VKH disease.

Correlation of serum amyloid A levels, clinical manifestations, treatment, and disease activity in patients with acute anterior uveitis.

PURPOSE: To investigate the association between serum amyloid A (SAA) protein and the clinical features of acute anterior uveitis (AAU), and to evaluate the disease activity and treatment effect in relation to SAA levels. METHODS: AAU patients and healthy individuals were recruited from October 2016 to August 2017 at the Department of Uveitis, in the Eye Hospital of Wenzhou Medical University. Related demographic, clinical characteristics, and therapeutic data were analyzed. RESULTS: One hundred and eight AAU patients and 18 healthy controls were included in this study. Serum SAA levels in AAU patients were significantly higher than those of healthy controls (p all < 0.0001). Significantly higher SAA levels were found in AS+AAU patients than those in AS-AAU patients (p < 0.05). SAA levels were also significantly higher in patients with HLA-B27+AAU compared with those with HLA-B27-AAU (p < 0.05). Furthermore, in each of the AAU subgroups, higher SAA levels were observed in the active state than those in the inactive state (p all < 0.05). In addition, SAA levels were positively correlated to anterior chamber cell counts (r = 0.492, p < 0.0001). ROC curve analysis revealed that SAA had an AUC value of 0.727 for detecting active inflammation (Youden's index = 0.38). SAA decreased with effective treatments (p = 0.0002). CONCLUSION: Serum levels of SAA were elevated in AAU patients. The increased levels of SAA were correlated with AS and HLA-B27 status. SAA levels were also positively correlated to disease activity and decreased with effective treatments. These findings suggest that SAA is associated with AAU, with a potential role in monitoring inflammatory processes and assessing the efficacy of therapy.