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Intravitreal Pharmacotherapies for Diabetic Macular Edema: A Report by the American Academy of Ophthalmology.
Ehlers, JP, Yeh, S, Maguire, MG, Smith, JR, Mruthyunjaya, P, Jain, N, Kim, LA, Weng, CY, Flaxel, CJ, Schoenberger, SD, et al
Ophthalmology. 2022;(1):88-99
Abstract
PURPOSE To review the evidence on the safety and efficacy of current anti-vascular endothelial growth factor (VEGF) and intravitreal corticosteroid pharmacotherapies for the treatment of diabetic macular edema (DME). METHODS Literature searches were last conducted on May 13, 2020, in the PubMed database with no date restrictions and limited to articles published in English. The combined searches yielded 230 citations, of which 108 were reviewed in full text. Of these, 31 were deemed appropriate for inclusion in this assessment and were assigned a level of evidence rating by the panel methodologist. RESULTS Only the 21 articles with level I evidence were included in this assessment. Seventeen articles provided level I evidence for 1 or more anti-VEGF pharmacotherapies, including ranibizumab (14), aflibercept (5), and bevacizumab (2) alone or in combination with other treatments for DME. Level I evidence was identified in 7 articles on intravitreal corticosteroid therapy for treatment of DME: triamcinolone (1), dexamethasone (4), and fluocinolone acetonide (2). CONCLUSIONS Review of the available literature indicates that intravitreal injections of anti-VEGF agents and corticosteroids are efficacious treatments for DME. Elevated intraocular pressure and cataract progression are important potential complications of corticosteroid therapy. Further evidence is required to assess the comparative efficacy of these therapies. Given the limited high-quality comparative efficacy data, choice of therapy must be individualized for each patient and broad therapeutic access for patients is critical to maximize outcomes.
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Rapid growth of primary uveal melanoma following intravitreal bevacizumab injection: a case report and review of the literature.
Ma, J, Roelofs, KA, Russell, L, Weis, E, Chen, SH
Digital journal of ophthalmology : DJO. 2021;(3):27-30
Abstract
Uveal melanoma size is a significant predictor of tumor metastasis. Although the relationship between antivascular endothelial growth factors (VEGF) and uveal melanoma growth has been studied, results are paradoxical, and the relationship remains controversial. We report the case of a 65-year-old man who presented with elevated intraocular pressure in his right eye, neovascularization of his iris, and significant corneal edema, which obscured the view of the angle. Given his history of proliferative diabetic retinopathy, he was diagnosed with neovascular glaucoma and subsequently received an intravitreal injection of bevacizumab and underwent Ahmed valve insertion. This was complicated by postoperative hyphema. Two and a half months postoperatively, a mass involving the inferior iris and ciliary body became visible, and fine-needle aspiration biopsy confirmed uveal melanoma. Seven weeks after diagnosis, the tumor's largest basal diameter had increased from 2.51 mm to 18.0 mm, and apical height increased from 6.23 mm to 11.0 mm. His right eye was enucleated. Histopathological analysis showed discontinuous invasion next to the Ahmed valve. Tumor progression after injection raises the possibility that in some untreated uveal melanomas, accelerated growth may occur following exposure to anti-VEGF agents.
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Medication Trends for Age-Related Macular Degeneration.
Cho, YK, Park, DH, Jeon, IC
International journal of molecular sciences. 2021;(21)
Abstract
Age-related macular degeneration (AMD) is central vision loss with aging, was the fourth main cause of blindness in 2015, and has many risk factors, such as cataract surgery, cigarette smoking, family history, hypertension, obesity, long-term smart device usage, etc. AMD is classified into three categories: normal AMD, early AMD, and late AMD, based on angiogenesis in the retina, and can be determined by bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E)-epoxides from the reaction of A2E and blue light. During the reaction of A2E and blue light, reactive oxygen species (ROS) are synthesized, which gather inflammatory factors, induce carbonyl stress, and finally stimulate the death of retinal pigment epitheliums (RPEs). There are several medications for AMD, such as device-based therapy, anti-inflammatory drugs, anti-VEGFs, and natural products. For device-based therapy, two methods are used: prophylactic laser therapy (photocoagulation laser therapy) and photodynamic therapy. Anti-inflammatory drugs consist of corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs). Anti-VEGFs are classified antibodies for VEGF, aptamer, soluble receptor, VEGF receptor-1 and -2 antibody, and VEGF receptor tyrosine kinase inhibitor. Finally, additional AMD drug candidates are derived from natural products. For each medication, there are several and severe adverse effects, but natural products have a potency as AMD drugs, as they have been used as culinary materials and/or traditional medicines for a long time. Their major application route is oral administration, and they can be combined with device-based therapy, anti-inflammatory drugs, and anti-VEGFs. In general, AMD drug candidates from natural products are more effective at treating early and intermediate AMD. However, further study is needed to evaluate their efficacy and to investigate their therapeutic mechanisms.
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Anti-vascular endothelial growth factor therapy in breast cancer: Molecular pathway, potential targets, and current treatment strategies.
Zhang, M, Liu, J, Liu, G, Xing, Z, Jia, Z, Li, J, Wang, W, Wang, J, Qin, L, Wang, X, et al
Cancer letters. 2021;:422-433
Abstract
As the highest incidence of female malignancy, breast cancer is likewise the leading cause of cancer-related deaths. The development of cancer relies on neo-vascularization, which provides sufficient nutrition and oxygen, and supplies a pathway for distant metastasis. Angiogenesis represents the formation of new blood vessels, and is a principal pathogenetic action in breast cancer. Vascular endothelial growth factor (VEGF) is a major angiogenesis regulator that modulates the maintenance and function of mature vascular networks. Therefore, the VEGF pathway is a promising oncotherapeutic target. This review elaborates an update on the prognostic value of VEGF in breast cancer, summarizes clinical experience and lessons of anti-VEGF therapeutics, meanwhile, provides an overview of biomarkers that predict the effectiveness of anti-angiogenic treatment.
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Vascular Endothelial Growth Factor, a Key Modulator of the Anti-Tumor Immune Response.
Geindreau, M, Ghiringhelli, F, Bruchard, M
International journal of molecular sciences. 2021;(9)
Abstract
During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.
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Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept.
González Astorga, B, Salvà Ballabrera, F, Aranda Aguilar, E, Élez Fernández, E, García-Alfonso, P, González Flores, E, Vera García, R, Fernández Montes, A, López Muñoz, AM, Salud Salvia, A
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2021;(8):1520-1528
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Abstract
Colorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient's profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.
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Updates on the Management of Ocular Vasculopathies with VEGF Inhibitor Conbercept.
Liu, H, Ma, Y, Xu, HC, Huang, LY, Zhai, LY, Zhang, XR
Current eye research. 2020;(12):1467-1476
Abstract
Purpose: To provide a detailed review on the therapeutic efficacy of conbercept for the management of ocular vasculopathies. Methods: A comprehensive literature search of various electronic databases was performed. Results: Ocular vasculopathy is one of the major causes of visual impairment and blindness which includes a range of disorders. Vascular endothelial growth factor (VEGF) regulates angiogenesis, enhances vascular permeability, and drives the formation of neovascularization. Anti-VEGF therapy has been shown to prevent vision loss or potentially improve vision in patients with exudative or neovascular retinal disease. The most recent anti-VEGF drug in China is conbercept. In the USA and Europe, bevacizumab is the most recently approved anti-VEGF agent. Conclusions: Conbercept serves as another anti-VEGF option for patients with neovascular AMD and other retinal vascular disorders. There have not been many clinical trials that study conbercept as compared with other currently available anti-VEGF drugs. There is a need for large-scale, well-designed, randomized clinical trials to ensure its long-term safety and efficacy and to determine if it has any advantages over other anti-VEGF agents.
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Regulation of Obesity by Antiangiogenic Herbal Medicines.
Shin, SS, Yoon, M
Molecules (Basel, Switzerland). 2020;(19)
Abstract
Obesity is the result of an energy imbalance caused by an increased ratio of caloric intake to energy expenditure. In conjunction with obesity, related metabolic disorders, such as dyslipidemia, atherosclerosis, and type 2 diabetes, have become global health problems. Obesity progression is thought to be associated with angiogenesis and extracellular matrix (ECM) remodeling. Angiogenesis occurs in growing adult adipose tissues, which are similar to neoplastic tissues. Adipose tissue is highly vascularized, and each adipocyte is nourished by an extensive capillary network. Adipocytes produce proangiogenic factors, such as vascular endothelial growth factor A and fibroblast growth factor 2, which promote neovascularization within the adipose tissue. Furthermore, matrix metalloproteinases (MMPs), including MMP-2 and MMP-9, play important roles in adipose tissue development and microvessel maturation by modifying the ECM. Thus, modulation of angiogenesis and MMP activity provides a promising therapeutic approach for controlling human obesity and its related disorders. Over the past decade, there has been a great increase in the use of alternative treatments, such as herbal remedies, for these diseases. This review will focus on the role of angiogenesis in adipose tissue growth and the regulation of obesity by antiangiogenic herbal medicines.
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Renal Toxicity of Systemic Therapy for Renal Cell Carcinoma.
Jaimes, EA
Seminars in nephrology. 2020;(1):49-58
Abstract
The incidence of kidney cancer has been increasing steadily and, until recently, there was a substantial lack of effective therapies for a cancer that is now among the 10 most common cancers in men and women. During the past 10 years, novel therapies have been developed including antiangiogenic drugs targeting vascular endothelial growth factor and its receptors, immune checkpoint inhibitors, and mammalian target of rapamycin inhibitors that have resulted in a significant improvement in clinical outcomes in a traditionally difficult-to-treat cancer. These new drugs, however, also have important side effects and toxicities that often have an impact on the treatment of these patients. The use of anti-angiogenic drugs often results in the development of hypertension and, less frequently, varying degrees of proteinuria including nephrotic range proteinuria. A variety of agents are used for the treatment of hypertension and proteinuria including blockers of the renin angiotensin system and calcium channel blockers, but there are no randomized clinical trials comparing different therapeutic agents in these patients. Immune checkpoint inhibitors have become one of the cornerstones of therapy in kidney cancer, but their use is linked to a variety of side effects that affect almost every organ and resemble autoimmune diseases. In the kidney, these drugs can induce acute interstitial nephritis in close to 5% of patients with varying degrees of severity that in some cases require discontinuation of treatment and systemic treatment with corticosteroids. Although mammalian target of rapamycin inhibitors now also are part of the therapeutic armamentarium available for these patients, all clinical trials have been performed in patients with normal renal function and therefore their effects in patients with abnormal renal function are not known.
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Curcumin: hopeful treatment of hemophilic arthropathy via inhibition of inflammation and angiogenesis.
Norooznezhad, F, Rodriguez-Merchan, EC, Asadi, S, Norooznezhad, AH
Expert review of hematology. 2020;(1):5-11
Abstract
Introduction: Hemophilic arthropathy (HA) is a serious complication among hemophilic patients causing a wide range of morbidity due to the inflammatory reactions followed by repeated episodes of bleeding. This condition has recently been shown to be accompanied by angiogenesis. The cascade starts with iron accumulation leading to an increase in CD68+ and CD11b+ cells responsible for initiating the inflammation.Areas covered: During inflammation, different factors and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor α (TNF-α) actively play parts in the pathogenesis of HA and also angiogenesis. It has been demonstrated that different pro-angiogenic and angiogenic factors such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), oxidative stress and matrix metalloproteinases (MMPs) are also important in the pathogenesis of HA. Curcumin is known for its strong anti-inflammatory and anti-angiogenic potentials. This agent is able to inhibit the mentioned inflammatory and angiogenic factors such as IL-1, IL-6, TNF-α, VEGF, MMPs, and HIF-1α. Also, as well as anti-angiogenic and anti-inflammatory activity, curcumin has a strong antioxidant potential and can decrease oxidative stress.Expert opinion: It seems that curcumin could be considered as a possible agent for the treatment of HA through inhibition of inflammation, oxidative stress, and angiogenesis.