Use Of anti-VEGF Drugs Research Articles

Effect of Anti-VEGF drugs on diabetic Retinopathy-Microaneurysms: A correlation study.

To investigate the efficacy of anti-vascular endothelial growth factor (VEGF) drugs in diabetic retinopathy (DR)-retinal microaneurysms, and its prognosis. This was a retrospectively study in which total of 120 patients with DR in Baoding No.1 Central Hospital from June 2020 to June 2022 were retrospectively analyzed. According to different treatment methods based on macular edema, they were divided into an injection group and a control group. The control group was treated routinely, while the injection group was additionally intravitreally injected with an anti-VEGF drug. The patients were followed up for one year, and the changes in the number of retinal microaneurysms, best corrected visual acuity (BCVA) and central retinal thickness (CRT) were compared between the two groups. The effect on retinal microaneurysms was analyzed. After treatment for 12 months, the total efficacy of the injection group was 95.00%, which was higher than 80.00% of the control group (p< 0.05). After one, three, six and twelve months of treatment, both CRT and the number of retinal microaneurysms reduced in the injection group compared with those before treatment. After treatment for one, three, six and twelve months, BCVA showed increases in the injection group, but no obvious changes in the control group compared with that before treatment. For patients with DR complicated with macular edema, early use of anti-VEGF drugs can significantly improve the fundus lesions, reduce the CRT and number of retinal microaneurysms, and improve the BCVA of the patients, with high clinical efficacy.

Anti-Vascular Endothelial Growth Factor Drugs for Age-Related Macular Degeneration

What Is the Issue?&#x0D; &#x0D; Wet age-related macular degeneration (AMD) is a serious health concern that causes reduced vision-related function, poor overall quality of life, and increased health care resource usage.&#x0D; Anti-vascular endothelial growth factor (VEGF) drugs are the first-line treatment for wet AMD, and they are injected into the eye. These drugs can slow disease progression but are expensive and require trained medical professionals to administer and monitor treatment response.&#x0D; The criteria for initial injection, maintenance, and discontinuation of anti-VEGF drugs in patients with wet AMD remain unclear.&#x0D; &#x0D; What Did We Do?&#x0D; &#x0D; To inform decisions about the appropriate use of anti-VEGF drugs to treat adults with wet AMD, CADTH sought to identify and summarize recommendations about criteria for the diagnosis of wet AMD and best practices for subsequent treatment with anti-VEGF drugs.&#x0D; An information specialist searched the peer-reviewed and grey literature for clinical practice guidelines published since 2018.&#x0D; &#x0D; What Did We Find?&#x0D; &#x0D; Three evidence-based guidelines recommend optical coherence tomography (OCT) to assess patients with suspected wet AMD. The National Institute for Health and Care Excellence (NICE) guidelines then strongly recommend fundus fluorescein angiography only when OCT does not exclude neovascular disease.&#x0D; The evidence-based guidelines recommend anti-VEGF drugs for wet or neovascular AMD in adults, particularly for patients with recent disease progression. One guideline suggests starting anti-VEGF treatment as soon as possible once the diagnosis of wet AMD is made.&#x0D; The NICE guideline suggests that there may not be any clinically significant distinctions in the effectiveness and safety of various anti-VEGF treatments, including aflibercept, bevacizumab, and ranibizumab, indicating a need for an individualized approach when selecting specific anti-VEGF drugs. However, 1 guideline is inconsistent with NICE, as it suggests choosing bevacizumab first.&#x0D; During the maintenance phase of using anti-VEGF drugs, it is important to closely monitor the patient's response and the disease activity and adjust the injection intervals accordingly.&#x0D; Guidelines recommend taking an individualized approach and emphasizing active patient involvement in switching and discontinuing anti-VEGF drugs for adults with wet AMD.&#x0D; Guidelines or guidance documents without a literature search or unclear methods provided generally consistent recommendations with the included evidence-based guidelines.&#x0D; We did not identify any evidence-based guidelines regarding the use of faricimab or brolucizumab. However, NICE published technology appraisals supporting the use of recently approved anti-VEGF drugs (faricimab and brolucizumab) as alternative options for patients who meet similar criteria for treatment with bevacizumab or aflibercept, and under agreed pricing conditions.&#x0D; &#x0D; What Does It Mean?&#x0D; &#x0D; All identified guidelines consistently recommend anti-VEGF drugs for adults with wet active AMD, with some providing guidance on the use of OCT and other ophthalmological assessments to identify criteria for starting and adjusting treatment.&#x0D; These guidelines recommend personalized and patient-centred approaches for selecting, switching, and discontinuing anti-VEGF medications. Cost is also a crucial factor in decision-making, especially for aflibercept, ranibizumab, and recently approved anti-VEGF drugs such as faricimab and brolucizumab.&#x0D; Further research and evidence-based guidelines are necessary to confirm whether newer drugs can be used in similar situations as older drugs.&#x0D;

Combined Use of Anti-VEGF Drugs Before and During Pars Plana Vitrectomy for Severe Proliferative Diabetic Retinopathy.

This study aimed to evaluate the combined administration of anti-vascular endothelial growth factor (anti-VEGF) drugs before and during pars plana vitrectomy (PPV) and to explore its efficacy and safety in the treatment of patients with severe proliferative diabetic retinopathy (PDR). This retrospective case series included consecutive patients who underwent PPV. Patients were categorized into two groups: the preoperative group was injected with anti-VEGF drugs before PPV, and the combination group was injected with anti-VEGF drugs before and during PPV. Preoperative, intraoperative, and postoperative clinical data were collected for analysis. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) and occurrence of postoperative vitreous cavity haemorrhage (POVCH). In total, 63 eyes of 60 patients with severe PDR were analysed. The operative duration and occurrence of intraoperative haemorrhage, iatrogenic retinal breaks, and silicone oil tamponade were similar between the two groups. The benefits on BCVA, and CRT after 1week postoperatively, were more obvious in the combination group (P < 0.01). Combination therapy had the potential to reduce the incidence of POVCH. No ocular or systemic adverse events occurred in either group. The combined use of anti-VEGF drugs before and during PPV in patients with severe PDR not only includes the advantages of preoperative injection, but also has more significant prognostic benefits and favourable safety profiles.

Risk factors and early biomarkers of nephrotoxicity associated with the use of anti-VEGF drugs.

e24079 Background: Anti-angiogenic anticancer drugs that block VEGF can cause kidney damage (Fujii et al., 2019). Among the mechanisms of nephrotoxicity thrombotic microangiopathy (TMA) of renal vessels can be distinguished (Estrada et al., 2019). TMA can be accompanied the development of anemia, excessive schistocytes, as well as increased LDH levels and a low platelet count, which indicated the occurrence of endothelial dysfunction and microangiopathic processes (Hauser et al, 2009). The goal of this study was to assess the risk factors of early nephrotoxicity and the utility of NGAL, KIM-1, HIF-1α and nephrin levels in urine as early biomarkers of nephrotoxicity. Methods: The study included 50 patients who received anti-VEGF drugs (aflibercept, bevacizumab or ramucirumab). Nephrotoxicity was determined as a decrease in glomerular filtration rate (GFR) to &lt; 60 ml/min/1.73m2 at 8 weeks from the initiation of therapy. The laboratory parameters and the levels of KIM-1, NGAL, HIF-1α and nephrin in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity we analyzed primary clinical and laboratory parameters. Results: Nephrotoxicity at 8 weeks was achieved in 21 (42%) of patients. A statistically significant decrease in hemoglobin and platelet count by 20 and 26%, respectively, from the initial level was observed. An increase in the number of schistocytes and a slight increase in LDH levels were also observed. The increase in NGAL, KIM-1 and nephrin levels was statistically significant in 1 weeks and the increase of HIF-1α in 2 weeks after the start of therapy (p = 0.001). The unfavorable predictors of nephrotoxicity as well as the favorable predictors in terms of decreasing renal function are presented in Table. ROC analysis demonstrated high sensitivity and specificity: NGAL – AUC 0.7; KIM-1 – AUC 0.69; HIF-1α – 0.7; nephrin – AUC 0.7. Conclusions: We report a significant increase in the parameters of microangiopathic hemolysis and in urine biomarkers of tubular and podocytic damage as well as hypoxia by the 8th week of treatment. We suggest that the TMA process can take part in renal damage. Increased levels of NGAL, KIM-1, HIF-1α and nephrin in the urine reflect the renal damage processes and have higher sensitivity and specificity then serum creatitine. The independent risk factors for nephrotoxicity are determined. [Table: see text]

Применение блокаторов ангиогенеза в комбинированном лечении неоваскулярной глаукомы

Neovascularization is the result of an imbalance between pro- and anti-angiogenic factors. Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic factors and its expression is enhanced in the ischemic retina. The study and introduction of VEGF inhibitors into the combined surgical treatment of neovascular glaucoma (NVG) in recent years have been of increasing interest to ophthalmologists. The review article presents an analysis of Russian and foreign literature on the use of anti-VEGF drugs (bevacizumab, ranibizumab, aflibercept and conbercept) in surgery of NVG, which are used «off-label» for this disease. The efficacy is evaluated and various methods of their administration are presented, as well as possible complications. The authors conclude that the most successful strategy in combined treatment of NVG is the use of antiangiogenic drugs, since in the vast majority of cases it allows to achieve the rapid disappearance or, at least, a significant regression of the iris rubeosis and reduction of hemorrhagic complications, which significantly improves the efficacy of subsequent surgical treatment of NVG. Keywords: neovascularization, anti-VEGF drugs, surgical treatment of neovascular glaucoma, prevention of hemorrhagic complications, improving the efficacy of surgical treatment

Evaluating the One-Year Efficacy of Combined Anti-VEGF and Dexamethasone Implant Treatment for Macular Edema in Retinal Vein Occlusions.

BACKGROUND Retinal vein occlusion-induced macular edema (RVO-ME) is a significant global cause of vision loss, with the effectiveness of combined anti-vascular endothelial growth factor (anti-VEGF) drugs and dexamethasone implantation (DEX I) being a relevant, yet not thoroughly explored, area of interest.The aim of this study was to evaluate the 1-year clinical efficacy of combination therapy using anti-vascular endothelial growth factor (VEGF) drugs and dexamethasone implantation (DEX I) in the treatment of macular edema secondary to retinal vein occlusion (RVO-ME). MATERIAL AND METHODS This retrospective study analyzed data from 34 RVO-ME patients treated at the Inner Mongolia Chaoju Eye Hospital between January 2020 and December 2021. All patients underwent initial DEX I treatment, followed by the introduction of anti-VEGF drugs, and were observed for one year. Retinal structural and vascular changes were measured using spectral domain optical coherence tomography (SD-OCT) and OCT angiography (OCTA). The study also evaluated shifts in best corrected visual acuity (BCVA) throughout the observation period. RESULTS Following the combined therapy, patients showed significant improvements in BCVA, intraocular pressure (IOP), central retinal thickness (CRT), and retinal vessel density (VD) (all P<0.05). Upon stratifying the results by RVO type, patients with branch retinal vein occlusion (BRVO)-ME displayed more significant BCVA improvement and CRT reduction at various post-treatment intervals compared to those with central retinal vein occlusion (CRVO)-ME (all P<0.05). CONCLUSIONS The combined use of anti-VEGF drugs and DEX I showed promising one-year efficacy in treating RVO-ME, with greater improvements noted in patients with BRVO-ME compared to those with CRVO-ME. Despite the positive results, close monitoring of IOP elevation, a notable side effect, remains crucial.

Роль блокады ангиогенеза у пациентов с диабетической ретинопатией

Relevance. The proliferative stage of diabetic retinopathy is characterized by angiogenesis, which is largely mediated by the vascular endothelial growth factor. Peripheral retinal laser coagulation has been standard treatment for PDR for many years, providing control of ischemia and reduction of vascular endothelial growth factor levels with subsequent regression of neovascularization. However, it leads to serious functional deficits and anatomical complications. The advent of antivascular endothelial growth factor (anti-VEGF) agents has changed the future of PDR management and has provided an alternative to pan retinal photocoagulation. Their combination with panretinal photocoagulation may be effective for the treatment of proliferative diabetic retinopathy and concurrent diabetic macular edema. Anti-VEGF therapy also takes place in surgery of complicated PDR. Purpose. To analyze the relevance of the use of anti-VEGF drugs in the treatment of the proliferative stage of diabetic retinopathy. Material and methods. The literature review is written using PubMed, Сochrane Library, 29 literature references published up to 2021. Results. In patients with severe cases, preoperative treatment is a gentle approach for the anatomic structures of the eye, it also contributes to the reduction in the number of intraoperative and postoperative complications. Conclusion. Preoperative treatment is a gentle approach for the anatomic structures of the eye, it also contributes to the reduction in the number of intraoperative and postoperative complications. Key words: anti-VEGF, diabetic macular edema, proliferative diabetic retinopathy.

Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS).

Background: The purpose of this study is to identify and characterize ocular adverse events (AEs) that are significantly associated with anti-VEGF drugs for treatment of neovascular age-related macular degeneration and compare the differences between each drug, and provide clinical reference. Methods: Ocular AEs submitted to the US Food and Drug Administration were analyzed to map the safety profile of anti-VEGF drugs. The Pharmacovigilance tools used for the quantitative detection of signals were reporting odds ratio and bayesian confidence propagation neural network. Results: A total of 10,608,503 AE reports were retrieved from FAERS, with 20,836 for ranibizumab, 19,107 for aflibercept, and 2,442 for brolucizumab between the reporting period of Q1, 2004 and Q3, 2021. We found and analyzed the different AEs with the strongest signal in each drug-ranibizumab-macular ischaemia (ROR = 205.27, IC-2SD = 3.70), retinal pigment epithelial tear (ROR = 836.54, IC-2SD = 7.19); aflibercept-intraocular pressure increased (ROR = 31.09, IC-2SD = 4.61), endophthalmitis (ROR = 178.27, IC-2SD = 6.70); brolucizumab-retinal vasculitis (ROR = 2930.41, IC-2SD = 7.47) and/or retinal artery occlusion (ROR = 391.11, IC-2SD = 6.10), dry eye (ROR = 12.48, IC-2SD = 2.88). Conclusion: The presence of AEs should bring clinical attention. The use of anti-VEGF drugs should be based on the patient's underlying or present medical condition to reduce any adverse event associated with the treatment.

Современный взгляд на лечение диабетического макулярного отека

Material and methods. When writing a literature review, data was searched on the PubMed and Scopus platforms for the period up to 2021 inclusive. The search was carried out using the following keywords: diabetic macular edema, Ozurdex, dexamethasone implant, antiVEGF, meta-analysis. A total of 33 articles were selected that are relevant to the topic of this literature review. Results. DME is one of the most common causes of vision loss in the world, especially in patients of working age. However, the choice of the treatment for DME is still controversial among vitreoretinal specialists. The pathophysiological process of DME development includes several mechanisms associated with chronic hyperglycemia. It has been proven that the level of vascular endothelial growth factor (VEGF) in the eye is not only elevated in DME, but is also proportional to the severity of edema. The use of anti-VEGF drugs for intravitreal administration for the treatment of DME has improved the prognosis of visual functions. The efficacy and safety of anti-VEGF drugs has been confirmed in many clinical studies. However, more and more data appear in the literature on the fairly common resistance to anti-VEGF therapy. Based on the foregoing, the experts concluded that it is necessary to revise the DME treatment strategy and conduct additional studies in order to identify other approaches in therapy to improve visual acuity. In patients with diabetes mellitus, high concentrations of pro-inflammatory cytokines were found. Corticosteroids have an anti-inflammatory effect, including reducing the permeability of the vascular walls, thereby giving an angiostatic effect in the treatment of DME. Thus, the dexamethasone implant may be a better alternative in the treatment of DME. Conclusion. Based on these studies, it can be concluded that the use of Ozurdex in the treatment of DME can be used both as the main treatment for DME and as an alternative treatment for patients who «poorly respond» to multiple injections of anti-VEGF drugs or in cases of resistance. Dexamethasone has the highest clinical efficacy among all corticosteroids used in ophthalmic practice, the drug demonstrates its multifaceted effects due to its influence on various links in the pathogenesis of DME. Dexamethasone implant reduces the concentration of both inflammatory cytokines in the eye and VEGF. Key words: diabetic macular edema, Ozurdex, dexamethasone implant, anti-VEGF

Эффективность анти-vegf терапии в авитреальных глазах у пациентов с диабетическим макулярным отеком: литературный обзор

Diabetic macular edema (DME) is a serious vision threating disease in patients with diabetes mellitus. The introduction of antivasoproliferative therapy (anti-VEGF) into ophthalmic practice allowed patients not only to maintain, but also significantly improve visual acuity. Patients with DME may also have ophthalmic complications that require surgery, such as 3-port pars plana vitrectomy. According to some data, at the time of the start of antiangiogenic therapy, 4.5% of patients with DMO have undegone vitrectomy. It is widely known that changing the environment in the vitreous cavity can have a significant impact on the pharmacokinetic parameters of angiogenesis inhibitors, and therefore affect their effectiveness in patients after vitrectomy. In this regard, the question arises concerning the effectiveness of the use of anti-VEGF drugs in vitrectomized eyes. The literature review contains current data from both pharmacokinetic studies of anti-VEGF drugs in animal models with vitrectomized eyes and clinical studies of antivasoproliferative therapy in patients with DME after vitrectomy. Key words: vitrectomy; diabetic macular edema; anti-VEGF; pharmacokinetics; aflibercept; ranibizumab; vitrectomized eyes.

Anti-VEGF Therapy in Ophthalmology

Angiogenesis is when the growth of new blood vessels occurs from the pre-existing vasculature, occurring in both healthy and pathological conditions.Usually, there is a balance maintained between angiogenesis regulators (angiogenesis promoting factors and angiogenesis inhibiting factors), but when this balance is lost, there is either too much or too little angiogenesis. VEGF (Vascular endothelial growth factor) and its receptor (VEGFR) are critical regulators of angiogenesis that promote it.It has been seen that it plays a significant role in the regeneration mechanism of blood vessels, inflammation of body tissues, cancer states, and wound healing. Various pathological conditions show increased VEGF activity.Nowadays, there has been increased use of anti-VEGF drugs, which target the vascular endothelial growth factor and slow down its action. The application of this therapy in ophthalmology is also becoming wider and wider. The implications of anti-VEGF dungs are cancers, rheumatological disorders, macular edema, various retinopathies, glaucoma, etc. &#x0D; Anti-VEGF treatment comprises of three main drugs, namely-Avastin, Lucentis, and Eylea. Their efficiency has been proven to be equal with varying manufacturing costs, packaging, and associated risks.These are the brand names for bevacizumab, ranibizumab, aflibercept, respectively, which have helped us achieve different milestones in treating all kinds of retinal diseases. Several other diseases like iris neovascularization, age-related macular degeneration (AMD), corneal diseases also have been treated using anti-VEGF drugs. Like all drugs, anti-VEGF drugs also have some limitations and side effects, including short half-life, systemic side effects; therefore, the development of new drugs still goes on.

Anti-VEGF therapy for diabetic retinopathy

Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, its treatment involves specialists of different areas - endocrinologists, diabetes specialists, therapists, cardiologists, surgeons, anesthesiologists etc. For ophthalmologists the objective is to diagnose ocular pathological changes associated with diabetes mellitus, and to prescribe required treatment in a timely manner. Treatment methods used in DR can be divided into three main groups: laser coagulation of the retina, intravitreal injection of medications - inhibitors of the vascular endothelial growth factor (VEGF) and glucocorticoids, as well as surgical treatment. The present literature review addresses the use of anti-VEGF drugs in the therapy of DR, specifically the latest medications, the most important studies on the treatment of DR and diabetic macular edema (DME), as well as post hoc analysis of such studies, the role of these medications in the therapy of refractory DME and proliferative stage DR. The review also addresses the upcoming strategies for therapy, as well as the importance of medications in prevention of DR and DME.

Update on the Use of Anti-VEGF Drugs in the Treatment of Retinopathy of Prematurity.

Retinopathy of prematurity (ROP) is one of the many significant consequences of premature birth and remains one of the leading causes of visual impairment in infants. Originally, cryotherapy was used to prevent the complications of vitreous hemorrhage and retinal detachment. Subsequently, laser photocoagulation, which is at least as effective and possibly safer than cryoretinopexy, was adopted as the primary treatment for type 1 ROP (stage 2 or 3 disease in zone II with plus disease or any stage disease in zone I with plus disease or stage 3 disease in zone I without plus disease). Laser therapy has been proven effective, and has a degree of permanence that is yet to be matched by alternative treatments, but can be associated with significant ocular side effects such as myopia. Treatment of type 1 ROP with anti-vascular endothelial growth factor (VEGF) agents seems to have fewer ocular side effects than laser ablation of the retina, particularly if used to treat type 1 ROP in zone I. However, ROP recurrence is a real threat after anti-VEGF therapy and long-term systemic side effects of this therapy remain under evaluation. This review focuses on the ophthalmic and systemic benefits and risks of anti-VEGF therapies for ROP as compared to retinal photocoagulation. Anti-VEGF therapies have dramatically altered the management of ROP and have also been shown to be beneficial with regard to the visual prognosis of patients with ROP, but patients so treated require frequent short- and long-term follow-up to detect and manage potential complications associated with this form of treatment. Such information also will allow clinicians to characterize the efficacy, side effect profile, and utility of intravitreal anti-VEGF agents for this condition. Prospective studies are needed to identify the optimum anti-VEGF drug and dose. [J Pediatr Ophthalmol Strabismus. 2020;57(6):351-362.].

HEMATOTOXIC ADVERSE DRUG REACTIONS ASSOCIATED WITH VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS AND CYTOTOXIC DRUGS IN THE TREATMENT OF GLIOBLASTOMA: A SYSTEMATIC REVIEW

Several studies have shown that the use of inhibitors of vascular endothelial growth factor (Vascular Endothelial Gowth Factor, VEGF) in the treatment of glioblastoma results in a significant increase in the rate of progression-free survival. However, administration of anti-VEGF agents is associated with the development of a wide range of adverse drug reactions (ADR), among which, hematotoxic ADR is the most common.The purpose of this study was to conduct a systematic review based on the results of randomized controlled clinical studies on the type and frequency of hematotoxic ADRs associated with anti-VEGF and chemotherapeutic agents in the treatment of glioblastoma.Material and Methods. Pubmed, EMBASE, Cohrane Library and eLibrary databases were used to identify reports from randomized controlled clinical studies on the safety of anti-VEGF drugs as the main/auxiliary treatment for patients with glioblastoma, and published from January 2008 to August 2019. The main criteria for inclusion of studies in the systematic review were determined.Results. The combined data analysis included 13 randomized controlled clinical trials. The average incidence of hematotoxic ADRs associated with anti-VEGF agents in monotherapy for glioblastoma was 27.7 %. Neutropenia and thrombocytopenia were the most common types of ADR. The average incidence of hematotoxic ADRs associated with cytotoxic drugs in monotherapy for glioblastoma was 48.1 %, and lymphopenia and thrombocytopenia were the main types of hematotoxic ADRs. The average incidence of hematotoxic ADRs associated with the combined use of anti-VEGF and chemotherapeutic drugs was 46.2 %. In this case, the most common ADRs were thrombocytopenia, neutropenia, and anemia. The use of a combination of anti-VEGF, chemotherapeutic drugs and radiation therapy was associated with the development of hematotoxic ADRs with an average incidence of 12.3 %. The most common ADR was severe thrombocytopenia.Conclusion. The use of anti-VEGF drugs as monotherapy for glioblastoma was associated with a lower incidence of hematotoxic ADRs. In this case, bevacizumab was the safest anti-VEGF agent in relation to hematotoxicity. The highest incidence of hematotoxic ADRs is observed for a combination of antiVEGF and cytotoxic drugs, such as cediranib with lomustine and bevacizumab with carboplatin.

Use of Anti-VEGF Drugs in Retinal Vein Occlusions.

Retinal vein occlusion (RVO) is one of the most prevalent causes of visual loss in the Western World. Its pathogenesis is still not completely known. Chronic macular edema and ischemia compromise the functional and anatomical status of the retina. Antivascular endothelial growth factor (anti-VEGF) injections have demonstrated better results than other previous options, including observation or laser therapy. This narrative review aims to analyze the current aspects related to these drugs.

Молекулярные и клеточные механизмы резистентности глиобластомы к ингибиторам фактора роста эндотелия сосудов

Представлен обзор современных источников литературы, посвященных изучению молекулярных и клеточных механизмов резистентности глиобластомы к антиангиогенным лекарственным средствам. Ангиогенез представляет собой важнейший патофизиологический механизм роста и прогрессирования глиобластомы за счет активного развития микрососудистой сети. Ускоренное развитие микрососудистой сети в глиобластоме происходит благодаря синтезу опухолевыми клетками большого количества фактора роста эндотелия сосудов (Vascular Endothelial Growth Factor, VEGF). Среди основных молекулярных и клеточных механизмов лекарственной устойчивости глиобластомы к анти-VEGF агентам принято относить VEGF-независимые пути ангиогенеза, активность клеток костного мозга и перицитов, а также сосудистую кооперацию, периваскулярную инвазию и феномен аутофагии. Изложены современные данные о рациональном и наиболее эффективном использовании анти-VEGF-лекарственных средств у пациентов с глиомами высокой степени злокачественности. Обозначены актуальные, остающиеся нерешенными вопросы, что обусловливает необходимость проведения дальнейших экспериментальных и клинических исследований, посвященных изучению механизмов лекарственной устойчивости глиобластомы к анти-VEGF-препаратам. This state-of-the-art review focuses on molecular and cellular factors associated with glioblastoma resistance to antiangiogenic drugs. Angiogenesis is an important pathophysiological mechanism for the growth and progression of glioblastoma facilitated by active development of microvasculature. The accelerated development of the microvascular network in glioblastoma occurs due to the synthesis of a large number of vascular endothelial growth factor (VEGF) by tumor cells Among the major molecular and cellular factors, glioblastoma drug resistance to anti-VEGF agents is commonly attributed to VEGF-independent pathways of angiogenesis, bone marrow cell and pericyte activity as well as to vascular co-option, perivascular invasion, and the phenomenon of autophagy. The authors provided current data on the rational and most effective use of anti-VEGF drugs for patients with high-grade gliomas. Relevant unsolved problems associated with drug resistance of glioblastoma to anti-VEGF drugs were highlighted.

Issues with Intravitreal Administration of Anti-VEGF Drugs.

PurposeTo provide an update of summary of risk factors and side effects of long-term use and contamination of intravitreal anti-VEGF injections.MethodsWe reviewed relevant publications of the topic of contamination of anti-VEGF injections and long-term side effects due to this reason.ResultsDue to the long-term use of anti-VEGF drugs and the higher number of injections worldwide, various studies have shown side effects in recent years, ranging from increased intraocular pressure to visual disturbing silicone oil vesicles in the vitreous cavity. Several studies have demonstrated that both the drug and the processing, storage, environmental factors and the material and design of the syringes have a decisive influence on these side effects.ConclusionThe risks of deposits from syringes in the eye can be significantly reduced by various optimizations in transport, storage and syringe and cannula selection.

EFFECTIVENESS OF VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN THE TREATMENT OF GLIOBLASTOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS

The purpose - was to perform a meta-analysis based on the results of randomized controlled trials that examined the efficacy and safety of using anti-VEGF (vascular endothelial growth factor (vascular endothelial growth factor, VEGF)) drugs as an auxiliary treatment for patients with glioblastoma (GBM). Material and methods. A search for randomized controlled trials was conducted in the Pubmed, EMBASE, eLibrary and Cohrane Library databases published from January 2008 to March 2019, which examined the efficacy and safety of using anti-VEGF agents as an auxiliary method of treating GBM patients. The odds ratio (OR) and 95% confidence interval (CI) were used to calculate the overall survival and progression-free survival values. Results. According to the eligibility criteria, 9 randomized controlled trials included in this meta-analysis that examine the results of using anti-VEGF drugs in 3189 patients with GBM. The overall survival rates of patients with GBM using anti-VEGF therapy exceed those in the group of patients with standard therapy without statistically significant differences (OR=0.89, 95% CI: 0.76, 1.04, p=0.13). Significant differences in progression-free survival were noted in favor of anti-VEGF agents (OR=0.70, 95% CI: 0.60, 0.82, p&lt;0.00001). The performed subgroup analysis showed the absence of a statistically significant effect of bevacizumab on the overall survival rates of patients with GBM (OR=0.89, 95% CI: 0.75, 1.06, p=0.20). Using a combination of bevacizumab and standard therapy can significantly improve the progression-free survival rates in patients with GBM (OR=0.63, 95% CI: 0.51, 0.78, p&lt;0.0001). Conclusion. The performed meta-analysis clearly demonstrated that the combination of anti-VEGF agents and standard therapy does not significantly increase the overall survival rate of patients with GBM. However, the use of anti-VEGF drugs statistically significantly improves the values of progression-free survival in patients with GBM.

The Role of Diet, Micronutrients and the Gut Microbiota in Age-Related Macular Degeneration: New Perspectives from the Gut⁻Retina Axis.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged ≥65 years in developed countries. Globally, it affects 30–50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many studies, such as the randomized controlled trials (RCTs) Age-Related Eye Disease Study (AREDS) and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high-fat and high-glucose or -fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

The synergistic effect of metformin and anti-vascular endothelial growth factor in the treatment of diabetic retinopathy

Objective To observe the synergistic effect of metformin and anti-vascular endothelial growth factor (VEGF) in the treatment of diabetic retinopathy. Methods This study was composed of clinical data review and in vitro cell experiment. Ten patients (12 eyes) with diabetic macular edema treated with anti- VEGF drugs were included in the study. Patients were randomly divided into the VEGF group (anti-VEGF drug therapy) and the combined treatment group (anti-VEGF drug combined with metformin). The changes of visual acuity and central retinal thickness (CRT) were compared between the two groups. As far as the in vitro experiment was concerned, vascular endothelial cells were divided into the control group (normal cells), the VEGF group (50 ng/ml VEGF), the anti-VEGF group (50 ng/ml VEGF+2.5 μg/ml of conbercept), and the combined group (50 ng/ml VEGF +2.5 μg/ml of conbercept +2.0 mmol/L of metformin). And then MTT cell viability assay, scratch assay and real-time quantitative polymerase chain reaction assay were performed to analyze the cell viability, cell migration and mRNA level of VEGFR2, protein kinase C (PKC)-α and PKC-β successively. Results Review of clinical trial shows that the CRT recovery rates in the combined treatment group were much higher than that in the VEGF group at 3 month after the operation, while the difference was statistically significant (t=−2.462, P<0.05). In vitro cell experiment results showed that VEGF induction upregulated the viability and mobility of vascular endothelial cells obviously compared with control group, at the same time, the use of anti VEGF drugs can effectively reverse the trend, in contrast, combination of metformin and anti-VEGF showed a more superior effect to some extent (P<0.05). In the VEGF group, the mRNA expression of VEGFR2, PKC-αand PKC-β were significantly increased compared with the control group (P <0.01); while the mRNA expression of VEGFR2, PKC-αand PKC-β in the combination group decreased significantly compared with the VEGF group and the control group (P<0.05). However, in the anti-VEGF group, the mRNA expression of VEGFR2, PKC-αand PKC-β were decreased, but has failed to reach the level of statistical learn the difference. Conclusions The combination of metformin and anti-VEGF drugs can reduce the CRT of diabetic retinopathy patients and inhibit the proliferation and migration of retinal vascular endothelial cells which induced by VEGF. The synergistic mechanism may be related to the inhibitory effect of metformin on the expression of VEGFR and PKC. Key words: Diabetic retinopathy/drug therapy; Metformin/therapeutic use; Angiogenesis inhibitors/therapeutic use; In vitro