Effect of anti-vascular endothelial growth factor on early-stage post-vitrectomy macular edema in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the effectiveness of anti-vascular endothelial growth factor (VEGF) therapy on post-vitrectomy macular edema (PVME) and determine the risk factors for PVME recovery. METHODS: This retrospective study included 179 eyes of 179 patients who underwent pars plana vitrectomy for proliferative diabetic retinopathy and developed PVME within 3 months after surgery. Eyes were grouped according to postoperative anti-VEGF treatment. RESULTS: Central retinal thickness (CRT) decreased significantly from baseline to 3-month follow-up in groups with (509.9 ± 157.2 µm vs. 401.2 ± 172.1 µm, P < 0.001) or without (406.1 ± 96.1 µm vs. 355.1 ± 126.0 µm, P = 0.008) postoperative anti-VEGF treatment. Best-corrected visual acuity (BCVA) did not differ between the two groups during follow-up. In the group not receiving anti-VEGF therapy, BCVA was significantly improved at 1, 2, and 3 months (P = 0.007, P < 0.001, and P < 0.001, respectively), while in the anti-VEGF group, BCVA was significantly improved at 1 and 3 months (P = 0.03 and P < 0.001). A thicker baseline CRT (ß = 0.44; 95% confidence interval, 0.26-0.61; P < 0.001) was significantly associated with decreasing CRT. CONCLUSION: PVME tends to spontaneously resolve in the early postoperative period. The effect of anti-VEGF therapy in the first 3 months after diagnosis appears to be limited.

RETINAL ARTERIAL MACROANEURYSM COMBINED WITH BRANCH RETINAL ARTERY OCCLUSION: Literature Review.

PURPOSE: To summarize the causes of retinal arterial microaneurysm combined with branch retinal artery occlusion. METHODS: The case reports of retinal arterial microaneurysm combined with branch retinal artery occlusion were searched in PubMed, Web of Science, and CNKI databases before May 1, 2024. A total of nine participants from nine case reports were included to analyze factors leading to complications. RESULTS: The reasons for this complication are as follows: complications during photocoagulation therapy. Intraretinal hemorrhage and exudation result in compression of adjacent or distal arteries, resulting in branch retinal artery occlusion. Embolus dislodgement or intraarterial embolus formation can block the artery, damage the wall, and provide conditions for the development of retinal arterial microaneurysm. In addition, it is necessary to be alert to the optic disk macroaneurysm, if hemorrhage or embolus formation in the macroaneurysm will affect the blood supply of the downstream artery, affecting a large range of the retina. CONCLUSION: Based on the review of case reports, we found that retinal arterial microaneurysm and branch retinal artery occlusion can cause each other. Acute vision loss can result when a complication occurs. In addition, retinal vascular diseases can reflect the whole body, suggesting that ophthalmologists need to pay attention not only to the patient's fundus but also to the patient's systemic diseases.

Use of intravitreal antiviral injection during vitrectomy in the treatment of acute retinal necrosis: anatomic and visual outcomes.

PURPOSE: To investigate whether intravitreal antiviral injection (IAI) during vitrectomy reduces the postsurgical retinal detachment (RD) rate and improves the visual prognosis of patients with acute retinal necrosis (ARN). METHODS: This retrospective cohort study included ARN patients treated at a tertiary hospital between January 2013 and December 2020. Patients who underwent pars plana vitrectomy (PPV) alone or combined with intraoperative IAI were classified in PPV-only group and PPV + IAI group, respectively. The incidence of postsurgical RD and the best corrected visual acuity (BCVA) between the groups was compared. A multivariate Cox hazard analysis was employed to explore the risk factors of postsurgical RD. A multivariate logistic regression analysis was applied to assess the impact of intraoperative IAI on preventing severe vision loss (SVL). RESULTS: Fifty-seven eyes with ARN with a median follow-up of 18.5 months were included in the study. There was no significant association between intraoperative IAI during vitrectomy and a reduced risk of postsurgical RD (hazard ratio [HR], 2.65; 95% CI, 0.71-9.89) or SVL at the 6-month follow-up visit (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.25-3.35). Better baseline best-corrected visual acuity (BCVA) was identified to associate with a higher risk of postsurgical RD (HR, 0.33; 95% CI, 0.14-0.81) and a lower risk of SVL at 6 months (OR, 2.28; 95% CI, 1.10-4.89). CONCLUSION: We did not observe a significant effect of intraoperative IAI on the anatomic and visual outcomes of ARN patients in this study. Intraoperative IAI may not be a necessary treatment option for ARN patients who receive vitrectomy.

Twelve-Month Outcomes of Three Episcleral Surgeries in Treatment of Rhegmatogenous Retinal Detachment.

INTRODUCTION: The aim of this study was to compare the long-term outcomes of conventional scleral buckling (CSB), modified scleral buckling (MSB), and scleral encircling (SE) in the treatment of rhegmatogenous retinal detachment and identify factors influencing the outcomes. METHODS: This comparative, retrospective cohort study assigned patients to CSB, MSB, and SE groups. The follow-up was 12 months, and the reattachment rate, complication rate, visual acuity, number of newly discovered tears during surgery, and changes in diopters were compared among the three surgeries. Influential factors on anatomical and functional reattachment were identified. RESULTS: There were no significant differences in the primary reattachment rate, overall complication rate, or best corrected visual acuity at 6 or 12 months among the three groups. The MSB group had a higher number of newly discovered tears during surgery compared with the other two groups. At 12 months of post-surgery, the SE group displayed the greatest change of diopter, whereas the MSB group showed the least change. The surgical approach did not influence the primary reattachment rate. Long-term visual outcomes were influenced by factors including sex, preoperative visual acuity, macular status, and duration of symptoms. CONCLUSION: MSB is an effective method for treating rhegmatogenous retinal detachment. Its advantages include the ability to identify smaller tears and induce minimal changes in diopter.

Discovery of Small-Molecule Inhibitors of the PD-1/PD-L1 Axis That Promote PD-L1 Internalization and Degradation.

Several monoclonal antibodies targeting the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway have been used successfully in anticancer immunotherapy. Inherent limitations of antibody-based therapies remain, however, and alternative small-molecule inhibitors that can block the PD-1/PD-L1 axis are urgent needed. Herein, we report the discovery of compound 17 as a bifunctional inhibitor of PD-1/PD-L1 interactions. 17 inhibits PD-1/PD-L1 interactions and promotes dimerization, internalization, and degradation of PD-L1. 17 promotes cell-surface PD-L1 internalized into the cytosol and induces the degradation of PD-L1 in tumor cells through a lysosome-dependent pathway. Furthermore, 17 suppresses tumor growth in vivo by activating antitumor immunity. These results demonstrate that 17 targets the PD-1/PD-L1 axis and induces PD-L1 degradation.

Progress in Redirecting Antiparasitic Drugs for Cancer Treatment.

Drug repurposing is a feasible strategy in developing novel medications. Regarding the cancer field, scientists are continuously making efforts to redirect conventional drugs into cancer treatment. This approach aims at exploring new applications in the existing agents. Antiparasitic medications, including artemisinin derivatives (ARTs), quinine-related compounds, niclosamide, ivermectin, albendazole derivatives, nitazoxanide and pyrimethamine, have been deeply investigated and widely applied in treating various parasitic diseases for a long time. Generally, their pharmacokinetic and pharmacodynamic properties are well understood, while the side effects are roughly acceptable. Scientists noticed that some of these agents have anticancer potentials and explored the underlying mechanisms to achieve drug repurposing. Recent studies show that these agents inhibit cancer progression via multiple interesting ways, inducing ferroptosis induction, autophagy regulation, mitochondrial disturbance, immunoregulation, and metabolic disruption. In this review, we summarize the recent advancement in uncovering antiparasitic drugs' anticancer properties from the perspective of their pharmacological targets. Instead of paying attention to the previously discovered mechanisms, we focus more on newly emerging ones that are worth noticing. While most investigations are focusing on the mechanisms of their antiparasitic effect, more in vivo exploration in clinical trials in the future is necessary. Moreover, we also paid attention to what limits the clinical application of these agents. For some of these agents like ARTs and niclosamide, drug modification, novel delivery system invention, or drug combination are strongly recommended for future exploration.

Triptolide laden reduced graphene oxide transdermal hydrogel to manage knee arthritis: in vitro and in vivo studies.

Triptolide (extract of herb Tripterygium wilfordii) is widely used in rheumatoid arthritis due to its potent immunosuppressant effect. The marketed oral (tablet dosage forms) and parenteral injections have short duration of action (half-life = 38 min) and not limited to multiorgan toxicity, which restrict the use of triptolide in clinical practice. In this study, a triptolide-loaded Pluronic® F68-reduced graphene oxide transdermal (non-invasive) hydrogel was developed to achieve sustained release of triptolide. Fourier transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy confirmed the synthesis of Pluronic® F68-reduced graphene oxide. Transmission electron microscopy showed flat wrinkled-nanosheets. The developed hydrogel showed desirable viscosity (11,261-11,365 cps), adhesiveness (0.25 mJ), hardness (6.5 g), and cohesiveness (1.85) for transdermal application. The ex vivo release study demonstrated the ability of the Pluronic® F68-reduced graphene oxide hydrogel to prolong release up to 14 h (63.64-96.78%), owing to the strong π-π interactions between the graphene oxide and the triptolide. The in vivo pharmacokinetic parameters in the rat model confirmed the improvement in the relative bioavailability (3.3-fold) with Pluronic® F68-reduced graphene oxide hydrogel in comparison to the control hydrogel without reduced graphene oxide. The anti-rheumatoid efficacy model suggest the potential application of Pluronic® F68-reduced graphene oxide hydrogel to treat knee rheumatoid arthritis (70-75% resolution) to substitute tablets and parenteral injections.

Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits.

Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. Since the ethyl acetate extract of C. aurantium dried immature fruits showed the highest xanthine oxidase inhibitory activity, chemical evidence for the potent inhibitory activity was clarified on the basis of structure identification of the active constituents. Five flavanones and two polymethoxyflavones were isolated and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, hesperetin showed more potent inhibitory activity with an IC50 value of 16.48 µM. For the first time, this study provides a rational basis for the use of C. aurantium dried immature fruits against hyperuricemia.

Bioassay-Guided Isolation and Identification of Xanthine Oxidase Inhibitory Constituents from the Leaves of Perilla frutescens.

Activity-directed fractionation and purification processes were employed to identify xanthine oxidase (XO) inhibitory compounds from the leaves of Perilla frutescens. The total extract was evaluated in vitro on XO inhibitory activity and in vivo in an experimental model with potassium oxonate-induced hyperuricemia in mice which was used to evaluate anti-hyperuricemic activity. The crude extract showed expressive urate-lowering activity results. Solvent partitioning of the total extract followed by macroporous resin column chromatography of the n-butanol extract yielded four extracts and eluted parts. Among them, only the 70% ethanol eluted part of the n-butanol extract showed strong activity and therefore was subjected to separation and purification using various chromatographic techniques. Five compounds showing potent activity were identified by comparing their spectral data with literature values to be caffeic acid, vinyl caffeate, rosmarinic acid, methyl rosmarinate, and apigenin. These results indicate that pending further study, these compounds could be used as novel natural product agents for the treatment of hyperuricemia.