Anti-vascular Endothelial Growth Factor Drugs Research Articles

The factors associated with retinal pigment epithelium tear development in the early phase after treatment initiation for age-related macular degeneration.

This study aimed to evaluate the factors associated with retinal pigment epithelium (RPE) tear development in the early phase after anti-vascular endothelial growth factor (VEGF) drug initiation in eyes with neovascular age-related macular degeneration (nAMD) and retinal pigment epithelial detachment (PED). Treatment-naive eyes with nAMD and PED for which anti-VEGF drug injections had been initiated and followed up for at least 3months after the 1st anti-VEGF drug injection, were retrospectively investigated. Baseline characteristics of the PEDs, including type, height, and area, were evaluated using fundus photographs, fluorescein angiography, and optical coherence tomography images. The association between patient age, sex, medical history, PED characteristics, and the development of RPE tears within 3months of starting anti-VEGF therapy was examined. This study included 244 eyes (230 patients; mean age 75.0years, 159 males and 71 females). RPE tears occurred in 13 eyes (5.3%) within 3months of the start of anti-VEGF therapy. Multivariate analysis showed an association of the development of RPE tears with PED height (every 100µm, odds ratio [OR]: 1.50, 95% confidence interval [CI]: 1.07-2.12, p = 0.019), PED area (every 10 mm2, OR: 3.02, CI: 1.22-7.46, p = 0.016), and the presence of fibrovascular PED (OR: 59.22, CI: 4.12-850.59, p = 0.002). Eyes with cleft (the hypo-reflective space beneath the fibrovascular PED) were more likely to develop an RPE tear (p = 0.01, χ-square test). Fibrovascular PED, large PED area, high PED height, and the cleft finding are independent risk factors for the development of RPE tears early after the administration of anti-VEGF drugs.

Novel CCR3-targeted cyclic peptides as potential therapeutic agents for age-related macular degeneration via inhibiting angiogenesis and reducing retinal photoreceptor damage

The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting CC motif chemokine receptor 3 (CCR3). Based on the binding mode of the N-terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development.

Proteomic study of vitreous in proliferative diabetic retinopathy patients after treatment with aflibercept: a quantitative analysis based on 4D label-free technique.

To identify different metabolites, proteins and related pathways to elucidate the causes of proliferative diabetic retinopathy (PDR) and resistance to anti-vascular endothelial growth factor (VEGF) drugs, and to provide biomarkers for the diagnosis and treatment of PDR. Vitreous specimens from patients with diabetic retinopathy were collected and analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analyses based on 4D label-free technology. Statistically differentially expressed proteins (DEPs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway representation and protein interactions were analyzed. A total of 12 samples were analyzed. The proteomics results showed that a total of 58 proteins were identified as DEPs, of which 47 proteins were up-regulated and 11 proteins were down-regulated. We found that C1q and tumor necrosis factor related protein 5 (C1QTNF5), Clusterin (CLU), tissue inhibitor of metal protease 1 (TIMP1) and signal regulatory protein alpha (SIRPα) can all be specifically regulated after aflibercept treatment. GO functional analysis showed that some DEPs are related to changes in inflammatory regulatory pathways caused by PDR. In addition, protein-protein interaction (PPI) network evaluation revealed that TIMP1 plays a central role in neural regulation. In addition, CD47/SIRPα may become a key target to resolve anti-VEGF drug resistance in PDR. Proteomic analysis is an approach of choice to explore the molecular mechanisms of PDR. Our data show that multiple proteins are differentially changed in PDR patients after intravitreal injection of aflibercept, among which C1QTNF5, CLU, TIMP1 and SIRPα may become targets for future treatment of PDR and resolution of anti-VEGF resistance.

Molecular mechanism and intervention measures of microvascular complications in diabetes.

In this article, the epidemiology, molecular mechanism of occurrence and development, risk factors, and treatment of diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy were discussed, providing the theoretical basis for more accurate elucidation of the pathogenesis and treatment of diabetic microvascular complications. The electronic database of PubMed was searched, and retrieved papers were screened for eligibility by two independent reviewers. Data were extracted using a standardized data extraction form and the quality of included papers was assessed. Thirty-eight articles were included. Diabetes nephropathy, diabetes peripheral neuropathy, and diabetes retinopathy are the most common and serious microvascular complications of diabetes in clinical patients. Renin-angiotensin system blockers, beta drugs, statins, antivascular endothelial growth factor drugs, and antioxidants can inhibit the occurrence of microvascular complications in diabetes. However, there has been no breakthrough in the treatment of diabetic microvascular complications. Therefore, prevention of diabetic microvascular complications is more important than treatment.

Clinical effects of atorvastatin combined with conbercept in the treatment of patients with macular edema secondary to retinal vein occlusion and carotid plaque: study protocol for a prospective randomized controlled trial.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs have been widely used in patients with macular edema (ME) secondary to retinal vein occlusion (RVO); however, recurrence is a major concern. This study aims to observe the clinical effects of atorvastatin and intravitreal therapy in the treatment of patients with branch or central RVO-ME and coexistent carotid plaques (CP). A prospective randomized controlled clinical trial will be conducted. Sixty-four patients diagnosed with branch or central RVO-ME and coexistent CP will be enrolled and randomly allocated in a 1:1 ratio to the control and experimental groups. The control group will be treated with intravitreal conbercept monthly for 3 months, followed by monthly evaluation and injection of pro re nata (PRN) for 12 months, while the experimental group will be treated with oral atorvastatin 20 mg daily combined with the control group treatment. If a drop of best-corrected visual acuity (BCVA) is more than five Early Treatment Diabetic Retinopathy Study (ETDRS) letters (one line) or an increment in central subfield thickness (CSFT) of 100 μm (or a 10% increment from the previous visit), intravitreal re-treatment will be performed. Outcome measurements include CSFT, BCVA, number of injections, and incidence of adverse events during the 12-month follow-up period. Differences between groups will be evaluated using Student's t-test, and comparisons between groups will be evaluated using repeated-measures analysis of variance. The study has been approved by the Institutional Review Board of Nanjing Lishui People's Hospital, Nanjing, China (approval number 2023KY0418-12, dated 18 April 2023), and has been registered on chictr.org.cn. Written informed consent will be collected from each patient and the results of this trial will be submitted to a peer-reviewed journal. Chinese Clinical Trial Registry ChiCTR2300071359. Registered on 12 May 2023.

Management after cataract surgery for patients with diabetic retinopathy: a systematic review and meta-analysis.

To evaluate the safety and effectiveness of various treatment modalities in patients with diabetic retinopathy (DR) who underwent cataract surgery. A comprehensive search for randomized controlled trials (RCTs) was conducted using the PubMed, Embase, Cochrane Library, and CNKI databases up to December 22, 2021. The safety and efficacy of treatment modalities were assessed using the risk ratio (RR) to compare the progression of DR and the mean difference to evaluate the best corrected visual acuity (BCVA) and macular thickness (MT). The meta-analysis of the RCTs revealed that anti-VEGF (anti-vascular endothelial growth factor) drugs significantly reduced the progression of DR [RR: 0.37 (95%CI 0.19, 0.70), P = 0.002] and improved BCVA [mean difference = -0.06 (-0.12, -0.01), P = 0.03] in patients with pre-existing DR who underwent cataract surgery. Steroid drugs also showed a significant reduction in macular thickness [mean difference = -55.63 (-90.73, -20.53), I2 = 56%, P = 0.002] in DR patients two weeks after cataract surgery compared to the control group. The safety profiles of different management options did not differ significantly. The present meta-analysis suggests that anti-VEGF drugs can effectively slow down the progression of diabetic retinopathy, improve BCVA, and reduce MT in DR patients who underwent cataract surgery. Steroid drugs also show promise in reducing MT. However, further studies with larger sample sizes are required to compare the efficacy and safety of different management options in a multi-center clinical setting.

Potential Mechanism of Platelet GPIIb/IIIa and Fibrinogen on Retinal Vein Occlusion

Purpose To explore the role of coagulation and fibrinolytic factors, and the potential mechanism of platelet aggregation in the pathogenesis of retinal vein occlusion. Methods Coagulation and fibrinolytic parameters in patients with retinal vein occlusion were determined using hemagglutinin and HISCL-5000. Relationships between these elevated parameters and factors representing typical clinical manifestations of retinal vein occlusion were examined, and these parameters were analyzed using a STRING database to indicate the potential role of platelet aggregation. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) levels were evaluated by flow cytometry after antiplatelet treatment in patients and mouse models. Furthermore, the GPIIb/IIIa ligand fibrinogen in peripheral blood and retina of mouse models was assessed by the turbidimetric method and real-time PCR, respectively. Results In patients, significant increases in peripheral blood fibrinogen and GPIIb/IIIa levels were observed (p = 0.0040, p < 0.0001, respectively). A positive correlation was observed between macular thickness (MT) and both fibrinogen and GPIIb/IIIa (r = 0.4528, p = 0.0063; r = 0.3789, p = 0.0427, respectively). After intravitreal injections of anti-vascular endothelial growth factor drugs, a significant reduction in fibrinogen levels was observed (p = 0.0072). In addition, the use of antiplatelet drugs resulted in a significant decrease in GPIIb/IIIa (p < 0.0001). In a mouse model, antiplatelet therapy significantly reduced both peripheral blood and retina fibrinogen levels and the overall rate of vein occlusion 3 days after occlusion (p < 0.0005). In addition, the reduction in GPIIb/IIIa levels after antiplatelet therapy was remarkable. Conclusion Fibrinogen and GPIIb/IIIa may be involved in retinal vein occlusion and blocking platelet aggregation may be a new therapeutic approach for retinal vein occlusion.

Kavain alleviates choroidal neovascularization via decreasing the activity of the HIF-1α/VEGF-A/VEGFR2 signaling pathway and inhibiting inflammation

Purpose: Neovascular age-related macular degeneration (nAMD) is a prevalent cause of blindness in the elderly. Standard treatment includes anti-vascular endothelial growth factor (VEGF) drugs, including Bevacizumab, Ranibizumab, and Aflibercept. However, anti-VEGF drugs may have limited efficacy and cause drug resistance. Recently, inflammation has been identified as one of the main risk factors in the progression of AMD. This study explores whether Kavain, an anti-inflammatory molecule from Piper methysticum, can treat choroidal neovascularization (CNV). Materials and methods: Various experiments were conducted to assess the Kavain’s toxicity. The impact of Kavain on in vitro cultured endothelial cells was examined through 5-Ethynyl-20-deoxyuridine (EdU) assays, transwell migration assays, and tube formation assays. The therapeutic effects of Kavain on CNV were investigated using a Laser-induced CNV mice model. Laser burns, approximately two papillary diameters away from the mouse optic nerve, were uniformly induced (532 nm wavelength, 0.1 s duration, 120 mW power, and 50 µm spot size). To elucidate the mechanism of Kavain, network pharmacology analysis, molecular docking, and western blots were performed. Results: Kavain exhibited no apparent toxicity both in vitro and in vivo. Kavain significantly decreased endothelial cell viability, proliferation, migration, and tube formation ability in a dose-dependent manner compared to the hypoxia groups (P&lt;0.05). Kavain alleviated CNV in the laser-induced CNV mouse model compared to the control groups (P&lt;0.05). These effects were statistically significantly enhanced in the Kavain plus Aflibercept groups (P&lt;0.05). Following Kavain administration, the expression levels of various inflammatory factors were markedly reduced in retinal pigment epithelium (RPE) /choroid complexes (P&lt;0.05). Mechanistically, we proved that Kavain decreased the activity of the hypoxia-inducible factor 1 α (HIF-1 α)/VEGF-A/VEGF receptor 2 (VEGFR2) signaling pathway. Conclusions: Our study is the first to demonstrate Kavain's potential as a promising treatment for nAMD, owing to its dual effects of anti-inflammation and anti-angiogenesis.

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management.

As an indispensable part of the human sensory system, visual acuity may be impaired and even develop into irreversible blindness due to various ocular pathologies. Among ocular diseases, fundus neovascularization diseases (FNDs) are prominent etiologies of visual impairment worldwide. Intravitreal injection of anti-vascular endothelial growth factor drugs remains the primary therapy but is hurdled by common complications and incomplete potency. To renovate the current therapeutic modalities, nanomedicine emerged as the times required, which is endowed with advanced capabilities, able to fulfill the effective ocular fundus drug delivery and achieve precise drug release control, thus further improving the therapeutic effect. This review provides a comprehensive summary of advances in nanomedicine for FND management from state-of-the-art studies. First, the current therapeutic modalities for FNDs are thoroughly introduced, focusing on the key challenges of ocular fundus drug delivery. Second, nanocarriers are comprehensively reviewed for ocular posterior drug delivery based on the nanostructures: polymer-based nanocarriers, lipid-based nanocarriers, and inorganic nanoparticles. Thirdly, the characteristics of the fundus microenvironment, their pathological changes during FNDs, and corresponding strategies for constructing smart nanocarriers are elaborated. Furthermore, the challenges and prospects of nanomedicine for FND management are thoroughly discussed.

Anti–Vascular Endothelial Growth Factor Drugs Compared With Panretinal Photocoagulation for the Treatment of Proliferative Diabetic Retinopathy: A Cost-Effectiveness Analysis

ObjectivesThis study aimed to evaluate the cost-effectiveness of anti–vascular endothelial growth factor drugs (anti-VEGFs) compared with panretinal photocoagulation (PRP) for treating proliferative diabetic retinopathy (PDR) in the United Kingdom. MethodsA discrete event simulation model was developed, informed by individual participant data meta-analysis. The model captures treatment effects on best corrected visual acuity in both eyes, and the occurrence of diabetic macular edema and vitreous hemorrhage. The model also estimates the value of undertaking further research to resolve decision uncertainty. ResultsAnti-VEGFs are unlikely to generate clinically meaningful benefits over PRP. The model predicted anti-VEGFs be more costly and similarly effective as PRP, generating 0.029 fewer quality-adjusted life-years at an additional cost of £3688, with a net health benefit of −0.214 at a £20 000 willingness-to-pay threshold. Scenario analysis results suggest that only under very select conditions may anti-VEGFs offer potential for cost-effective treatment of PDR. The consequences of loss to follow-up were an important driver of model outcomes. ConclusionsAnti-VEGFs are unlikely to be a cost-effective treatment for early PDR compared with PRP. Anti-VEGFs are generally associated with higher costs and similar health outcomes across various scenarios. Although anti-VEGFs were associated with lower diabetic macular edema rates, the number of cases avoided is insufficient to offset the additional treatment costs. Key uncertainties relate to the long-term comparative effectiveness of anti-VEGFs, particularly considering the real-world rates and consequences of treatment nonadherence. Further research on long-term visual acuity and rates of vision-threatening complications may be beneficial in resolving uncertainties.

Multiple Choroidal Neovascularizations in Choroidal Osteoma Treated with Anti-VEGF Injections: A 6-Year Follow-Up Case Report.

To report a case of multiple choroidal neovascularizations (CNVs) secondary to choroidal osteoma injected with a total of 13 anti-vascular endothelial growth factor (VEGF) drugs over a long-term follow up of 6-year period. Case report. A 29-year-old female presented with a peripapillary choroidal osteoma in her left eye with the best-corrected visual acuity (BCVA) of 20/25. After 2 years of follow-up, two foci of CNV (one was at the infra-nasal of the optic disc, and the other was near the sub-temporal vascular arch), and massive subretinal hemorrhage developed overlying the osteoma, causing decreased BCVA of 20/33. The patient was treated with four consecutive intravitreal injections of conbercept and the two CNVs regressed with BCVA recovered to 20/25. While 17 months later, the third CNV lesion locating at the fovea appeared and nine more injections of aflibercept were given during which repeated recurrence of it occurred. At last follow-up, 6 years from baseline, all the three CNV foci were controlled, with final BCVA of 20/33. Multiple CNVs may appear simultaneously at different locations in one osteoma and prompt treatment with intravitreal anti-VEGF may be a good option to control the progression and recurrence of these CNVs. Long-term follow-up and multimodal imaging are vital in the management of CO-associated CNV.

BROLUCIZUMAB FOR WET-AGED RELATED MACULAR DEGENERATION PATIENTS : TOO GOOD TO BE TRUE

Introduction &amp; Objective: Brolucizumab is the newest anti-vascular endothelial growth factor (anti-VEGF) drug. It showed superior anatomic outcomes compared to other anti-VEGF and noniferiority best corrected visual acuity (BCVA) results for Wet-Aged Related Macular Degeneration (Wet-AMD) patients. In Yogyakarta, its been only used in few patients and we want to report the Effectiveness and safety of brolucizumab in Wet-AMD patients in Yogyakarta. Method: In this retrospective study, all neovascular AMD (nAMD) Patients who underwent brolucizumab intravitreal injections between December 2021 and January 2023 at YAP Eye Hospital were studied. Patient’s demographic data, before and after intravitreal brolucizumab injections (central subfield thickness, intraocular pressure and BCVA) were assessed. Result :This study included 6 eyes of 6 patients ( 3 women) with a mean age of 69.5 years old. The mean follow- up period was 27 ± 10.1 weeks after the first injection of brolucizumab. Three patients were naïve nAMD patient, never got any intravitreal injections and three anti-VEGF experienced nAMD patients with ranibizumab or aflibercept injections prior to brolucizumab. Mean BCVA at baseline (before brolucizumab injection) was 0.12 decimal (6/48) and was 0.29 decimal (6/20) at the last follow-up. Five out of six patients visual acuity were improved,one patient had constant bcva. Four out of six patient central subfield thickness were reduced, none of the patient intraocular pressure increased over 21 mmhg. None of the patient reported any signs of inflammation, vasculitis, or any other ocular or systemic adverse effects. Conclusion :This limited data demonstrated that brolucizumab was safe and effective in stabilizing BCVA for both of nAMD patients who had undergone previous treatment with other anti-VEGFs agents and naive. Future larger multicenter collaborative studies are warranted.

Current Trends in Diagnosis and Treatment Approach of Diabetic Retinopathy during Pregnancy: A Narrative Review.

Diabetes mellitus during pregnancy and gestational diabetes are major concerns worldwide. These conditions may lead to the development of severe diabetic retinopathy during pregnancy or worsen pre-existing cases. Gestational diabetes also increases the risk of diabetes for both the mother and the fetus in the future. Understanding the prevalence, evaluating risk factors contributing to pathogenesis, and identifying treatment challenges related to diabetic retinopathy in expectant mothers are all of utmost importance. Pregnancy-related physiological changes, including those in metabolism, blood flow, immunity, and hormones, can contribute to the development or worsening of diabetic retinopathy. If left untreated, this condition may eventually result in irreversible vision loss. Treatment options such as laser therapy, intravitreal anti-vascular endothelial growth factor drugs, and intravitreal steroids pose challenges in managing these patients without endangering the developing baby and mother. This narrative review describes the management of diabetic retinopathy during pregnancy, highlights its risk factors, pathophysiology, and diagnostic methods, and offers recommendations based on findings from previous literature.

Clinical efficacy of subthreshold micropulse laser combined with anti-VEGF drugs in the treatment of diabetic macular edema: A meta-analysis.

To systematically evaluate the efficacy and safety of subthreshold micropulse laser (SML) combined with anti-vascular endothelial growth factor (VEGF) drugs for the treatment of diabetic macular edema (DME). The randomized controlled trials on SML combined with anti-VEGF drugs for DME were retrieved from China National Knowledge Infrastructure, Wan Fang Data, VIP Data, Sino Med (China Biomedical Literature Database), PubMed, Web of Science, The Cochrane Library, and Embase by computer from inception to April 19, 2022. The observation group was treated with SML combined with anti-VEGF drugs, while the control group was treated with anti-VEGF agents alone or SML. And the references of the included literature were manually searched. The Meta-analysis was performed using Revman 5.4 and STATA SE 15. This study finally included 15 randomized controlled trials involving 891 eyes for Meta-analysis. The results showed that there was no statistically significant difference between the 2 groups in best-corrected visual acuity at 1, 3, 6, 9, and 12 months after treatment. There was no statistical difference between the 2 groups in central macular thickness (CMT) at 1, 3, and 6 months after treatment (P > .05). CMT in the observation group was lower than that in the control group at 9 and 12 months (P < .05). There was no statistical difference between the 2 groups in total macular volume at 3, 6, 9, and 12 months in CMT (P > .05). The number of anti-VEGF drugs injections in the observation was lower than that in the control group (P < .05). The occurrence of complications between the 2 groups was not statistically significant difference (P > .05). SML in combination with anti-VEGF drugs in patients with DME are comparable in reducing the number of anti-VEGF drugs injections and CMT, thereby reducing the financial burden on patients. It does not differ in best-corrected visual acuity and total macular volume.

The Effect of Systemic Parameters and Baseline Characteristics in Short-Term Response Analysis with Intravitreal Ranibizumab in Treatment-Naive Patients with Neovascular Age-Related Macular Degeneration.

Anti-vascular endothelial growth factor drugs keep being the main therapy for neovascular age-related macular degeneration (AMD). Possible predictive parameters (demographic, biochemical and/or inflammatory) could anticipate short-term treatment response with ranibizumab. 46 treatment-naive patients were included in a prospective observational study. They underwent three monthly injections of intravitreal ranibizumab for neovascular AMD and the clinical examination was made at baseline and one month after the third injection. Demographic characteristics, co-morbidities and concomitant treatments were recorded at the baseline visit. Biochemical parameters, complete blood count and inflammation biomarkers were also measured at these times. Uric Acid was found to be statistically significant with a one-point difference between good and poor responders in both basal and treated patients, but only in basal parameters was statistical significance reached (p = 0.007 vs. p = 0.071 in treated patients). Cholesterol and inflammatory parameters such as white blood cell count and neutrophils were significantly reduced over time when treated with intravitreal ranibizumab. On the other hand, women seemed to have a worse prognosis for short-term response to intravitreal ranibizumab treatment. Uric acid may help identify possible non-responders before initial treatment with ranibizumab, and cholesterol and white blood cells could be good candidates to monitor short-term response to ranibizumab treatment.

Topical Application of Cell-Penetrating Peptide Modified Anti-VEGF Drug Alleviated Choroidal Neovascularization in Mice.

Age-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy. Two complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments. Both 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts. In this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD.

망막 혈관 질환에서 원형 RNA의 작용 기전 및 RNA 치료제로서의 가능성

Maintaining and preserving visual function became critical in this aging society. The number of patients with retinal vascular disease such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy is gradually increasing due to increased life expectancy, advancements in the technology of delivering premature babies, and complications due to eating habits. To treat these retinal vascular diseases, surgical intervention such as laser photocoagulation and anti-vascular endothelial growth factor (VEGF) drugs can be considered. However, these treatment options are accompanied by various complications and adverse effects. Thus, new treatments focusing on the pathogenesis of retinal vascular disease need to be developed. Various evidences suggest that circular RNA is involved in the pathogenesis of retinal disease. In this article, we discuss about currently used treatments of retinal vascular diseases and the emerging role of circular RNAs in the pathogenesis of retinal vascular diseases. Therefore, understanding the mechanism of circular RNA regulating retinal disease and developing therapeutics using these circular RNAs may offer novel treatment options to cure retinal vascular disease.

Efficacy of four anti-vascular endothelial growth factor agents and laser treatment for retinopathy of prematurity: A network meta-analysis.

This study undertakes a comprehensive comparison of five different interventions for the treatment of type-1 retinopathy of prematurity (ROP) and aggressive posterior retinopathy of prematurity (APROP), offering insights into their relative efficacies and contributing to better clinical decision-making. The aim of this study was to compare the efficacy of intravitreal aflibercept (IVA), intravitreal bevacizumab (IVB), intravitreal conbercept (IVC), intravitreal ranibizumab (IVR), and laser therapy in treating these conditions. We conducted a search for relevant randomized controlled trials (RCTs) in databases, namely PubMed, Embase, Cochrane Library, Web of Science, and Ovid, focusing on these five treatment modalities for ROP. The quality of included studies was evaluated using the Cochrane Risk of Bias Assessment Tool, and data analysis was performed using STATA software. The results from our network meta-analysis (NMA) indicated that IVA significantly prolonged the interval between initial treatment and relapse in patients, with a surface under the cumulative ranking cruve (SUCRA) value of 99.1%. Additionally, patients in the IVB group had a significantly higher spherical equivalent refraction (SER) after surgery, with a SUCRA value of 84.4%. Furthermore, IVR was the most effective in reducing the duration of peripheral retinal vascularization, with a SUCRA value of 95.6%. However, no statistically significant differences were found in relapse rates among the five treatment options. Our analysis concludes that intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drug monotherapy generally offer better outcomes than laser treatment for ROP. Nonetheless, additional RCTs are necessary to further evaluate the safety of anti-VEGF agents.

Macular Neovascularization Type Influence on Anti-VEGF Intravitreal Therapy Outcomes in Age-Related Macular Degeneration

PurposeTo evaluate the influence of macular neovascularization (MNV) lesion type on 12 months clinical outcomes in treatment-naïve eyes with age-related macular degeneration (nAMD) eyes treated with anti-vascular endothelial growth factor (VEGF) drugs nationwide. DesignMulticenter national nAMD database observational study. SubjectsOne thousand six-hundred six treatment-naïve nAMD eyes (1330 patients) undergoing Anti-VEGF therapy for 12 months nationwide. MethodsDemographics, visual acuity (VA) in logarithm of the minimum angle of resolution (logMAR) letters, number of injections and visits data was collected using a validated web-based tool. Neovascular lesion phenotype was classified as type 1 (T1, n=711), type 2 (T2, n=505), type 3 (T3, n=315) and aneurysmal type 1 (A-T1, n=75), according to the new proposed consensus classification. Main outcome measuresMean VA change at 12 months, final VA at 12 months, number of injections, time to lesion inactivation. ResultsA total of 1606 treatment-naïve nAMD eyes (1330 patients) received a median of 7 injections over 12 months. Mean (±standard deviation) baseline VA was significantly lower for T2 (49.4±23.5 letters) compared to T1 (57.8±20.8) and T3 (58.2 ±19.4)(both p<0.05) lesions. Mean VA change at 12 months was significantly greater for A-T1 (+9.5 letters) compared to T3 (+3.1 letters, p<0.05). T3 lesions had fewer active visits (24.9%) than the other lesion types (T1 30.5%, T2 32.6%, A-T1 27.5%, all p<0.05). Aflibercept was the most used drug in A-T1 lesions (70.1%) and ranibizumab in T1 (40.7%), T2 (57.7%) and T3 (47.6%) lesions. ConclusionsThis study highlights the relevance of MNV type on clinical outcomes in nAMD and reports significant differences in baseline VA, VA change and lesion activity at 12 months. This report provides data about lesion-specific clinical features, which may guide the management of nAMD cases and potentially support a personalized clinical decision making in these patients.

Hematologic and lymphatic system toxicities associated with immune checkpoint inhibitors: a real-world study.

Introduction: Immune checkpoint inhibitors (ICIs) exert antitumor responses in many types of cancer but may also induce serious or fatal toxicities that affect all organ systems, including the hematologic and lymphatic systems. However, the risk of hematologic and lymphatic system toxicities following different ICI treatments remains unknown. This study aimed to describe the hematologic and lymphatic system toxicities associated with different ICI regimens and the impact of combining ICIs with anti-vascular endothelial growth factor drugs using the United States Food and Drug Administration Adverse Event Reporting System pharmacovigilance database. Methods: The reporting odds ratio (ROR) and information component (IC) indices were used to identify disproportionate reporting of ICI-associated hematologic and lymphatic adverse events (AEs). Results: We extracted 10,971 ICI-associated hematologic and lymphatic AEs from 35,417,155 reports. These AEs were more frequently reported in female patients (ROR: 1.04 95% confidence interval [CI]: 1.01-1.07) and younger patients (ROR: 1.05 95% CI: 1.01-1.09). The disseminated intravascular coagulation fatality rate (63.97%) was the highest among the reported preferred terms, despite its low incidence (3.32%). The time to onset of ICI-related hematologic and lymphatic AEs was relatively short, with 77.44% reported within 3months. Disproportionate analysis showed that most ICIs were associated with significant overreporting of hematologic and lymphatic AEs (IC025: 0.34 and ROR025: 2.10). Hematologic and lymphatic system AEs were more frequently reported in patients treated with anti-programmed cell death protein 1/programmed cell death ligand 1 monotherapy than in those treated with anti-cytotoxic T-lymphocyte-associated protein 4 monotherapy (ROR: 1.54, 95% CI: 1.38-1.71), with atezolizumab showing the strongest signal (ROR025: 4.19, IC025: 1.00). In patients receiving combined treatment, ICIs plus bevacizumab exerted a higher disproportion signal than monotherapy (ROR: 161, 95% CI: 1.75-1.88). Discussion: The spectrum of hematologic and lymphatic AEs differed according to the ICI regimen. Early recognition and management of ICI-related hematologic and lymphatic AEs are vital in clinical practice.