Effects of subconjunctivally injected bevacizumab, etanercept, and the combination of both drugs on experimental corneal neovascularization

Özdemir, Özdemir; Altıntaş, Özgül; Altıntaş, Levent; Yıldız, Demir Kürşat; Sener, Ender; Çağlar, Yusuf

doi:10.1016/j.jcjo.2012.12.003

Cited by 27 publications

(19 citation statements)

References 34 publications

(44 reference statements)

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“…Etanercept, an inhibitor of tumor necrosis factor, has been approved by Food and Drug Administration (FDA) to treat rheumatoid arthritis (RA), JIA and other arthritic diseases (Kerensky et al 2012). However, etanercept can cause serious side effects: new infections (Chiang et al 2014); nervous system problems including multiple sclerosis (Gomez-Gallego et al 2008), seizures or eyes inflammation (Ozdemir et al 2013;Saeed et al 2014); blood problems (van Denderen et al 2012); heart failure (Kerensky et al 2012); allergic reactions (Kato et al 2006); a lupus-like syndrome (Araki et al 2011); and autoimmune hepatitis (Toulemonde et al 2012). All the unwanted adverse effects limit its usage in JIA therapy.…”

Section: Introductionmentioning

confidence: 99%

Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study

Zhong

Wang

Guo

et al. 2015

Tohoku J. Exp. Med.

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Juvenile idiopathic arthritis (JIA) is the most common arthritis in the adolescents under the age of 16. Etanercept, an inhibitor of tumor necrosis factor, is often used to treat JIA despite its significant side effects. Homeopathic remedies, such as blueberries, have anti-inflammatory properties with fewer unwanted effects and should be considered as a primary treatment. We aimed to explore the efficacy and safety of combination therapy of blueberry and etanercept for JIA. Two hundred and one JIA patients were selected, and randomly and evenly assigned to three groups: ETA (50 mg of etanercept twice weekly), ETABJ (matched etanercept and 50 ml blueberry juice daily) and ETAPJ (matched etanercept and placebo juice). The severity of JIA was measured using American College of Rheumatology scales (ACR) 20, 50 and 70. The levels of pro-inflammatory cytokines, interleukin-1 (IL1) alpha and IL1 beta, and interleukin-1 receptor antagonist (IL1RA) were measured by qRT-PCR and ELISA. After a 6-month follow-up, the ACR20, ACR50 and ACR70 in an ETABJ group were higher than those in other two groups (P < 0.05), suggesting clinically meaningful improvement in JIA. Meanwhile, the symptoms and side effects were reduced significantly or absent in an ETABJ group, including mental diseases, retrobulbar optic neuritis, gaining weight, infection, cutaneous vasculitis, diarrhea, uveitis and pancytopenia. Blueberries reduced the levels of IL1 alpha and beta, and increased the level of IL1RA. Thus, a combination therapy of blueberry and etanercept can reduce the severity of JIA and should be developed as a new method for JIA therapy.

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Section: Introductionmentioning

confidence: 99%

Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study

Zhong

Wang

Guo

et al. 2015

Tohoku J. Exp. Med.

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“…It is upregulated under conditions of neovascularization and it plays an important role in the development of pathological angiogenesis in inflammatory, neoplastic, and vascular diseases of the eye. Numerous studies have shown that anti-VEGF agents, used either alone or in combination with steroids, verteporfin, or anti-tumor necrosis factor-α microantibody, are effective in the treatment of corneal neovascularization (17) . Anti-VEGF agents reported for the treatment of corneal neovascularization include bevacizumab, pegaptanib, and , fibroblasts (black thick arrow), blood vessels, and stained erythrocytes within the blood vessels (white thick arrow) can be seen.…”

Section: Discussionmentioning

confidence: 99%

“…who was blinded to the study groups. The following scaling system, previously described in a study on corneal neovascularization, was used ( Figure 4) (15) …”

Section: Methodsmentioning

confidence: 99%

Comparison of the effects of subconjunctival and topical anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization

Özdemir¹,

Altıntaş²,

Altıntaş³

et al. 2014

Arquivos Brasileiros De Oftalmologia

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Purpose: To compare the effects of bevacizumab applied either subconjunctivally or topically, in a rat model of corneal neovascularization induced by alkali burn. Methods: The right corneas of 24 Wistar-Albino rats were cauterized with silver nitrate sticks. The rats were divided randomly and equally into three groups: no treatment control (n=8), subconjunctival bevacizumab treatment (n=8), and topical bevacizumab treatment (n=8). Immediately following cauterization, the subconjunctival group was treated with a 0.05 ml (1.25 mg) bevacizumab subconjunctival injection. The topical group was treated with 10 mg/ml bevacizumab twice daily, and the control group received subconjunctival saline injections twice daily. The burn stimulus and neovascularization scores were evaluated using a technique previously described by Mahoney and Waterbury. Digital photographs were obtained before the eyes were enucleated and corneal sections were then analyzed by histopathology. Results: The mean burn stimulus score was 1.86 ± 0.6 and there was no statistical difference between the groups (p=0.730). The mean neovascularization scores in the subconjunctival and topical bevacizumab groups were statistically lower than the control group (p<0.05). The mean percentage area of corneal neovascularization was 82.5 ± 22.1 in the control group, 42.7 ± 15.0 in the subconjunctival group, and 55.8 ± 18.2 in the topical group. The differences between the control and treatment groups were statistically significant (p<0.05). Histopathology showed that the treatment groups presented less neovascularization, inflammation, and fibroblast activity than the control group (p<0.05). Conclusions: This study demonstrates that both subconjunctival and topical administrations of bevacizumab inhibit corneal neovascularization and decrease inflammation and fibroblast activity in a rat model of corneal neovascularization induced by alkali burn.

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“…[58][59][60][61] With regard to CNV, it has been recently demonstrated that subconjunctivally injected etanercept has significant antiangiogenic and anti-inflammatory effects in the treatment of CNV in a rat model of burned cornea. 62 Adalimumab Adalimumab has been proposed for the treatment of Mooren ulcer, 63 as an alternative to infliximab treatment. 64 Alzaga Fernandez et al 65 showed healing of interstitial keratitis, not adequately controlled with topical steroids, after systemic adalimumab treatment.…”

Section: Etanerceptmentioning

confidence: 99%

Tumor Necrosis Factor-α Inhibitors as a Treatment of Corneal Hemangiogenesis and Lymphangiogenesis

Ferrari

Bignami

Rama

2015

Eye &Amp; Contact Lens: Science &Amp; Clinical Practice

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The cornea is normally devoid of blood and lymphatic vessels; however, a number of infectious/inflammatory diseases can induce corneal neovascularization (CNV). Tumor necrosis factor (TNF)-α, a well known pro-inflammatory cytokine, acts on the vascular endothelium by promoting vasodilatation, edema, and leukocyte recruitment, which are all commonly associated with the development of CNV. Corneal neovascularization is the second cause of blindness worldwide; hence, pharmacological TNF-α inhibition might represent an attractive therapeutic option. Although none of the existing TNF-α antagonists has been registered as a CNV inhibitor, three of them (etanercept, adalimumab, and infliximab) have been proposed to control ocular inflammation. More specifically, it has been demonstrated that infliximab is also effective in reducing hemangiogenesis and lymphangiogenesis in different animal models of CNV. In this article, we review the role of TNF-α on the ocular surface and, in particular, its specific role in the process of CNV. Moreover, we review existing literature and speculate on the potential role of TNF-α inhibitors in the treatment of CNV.

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Effects of subconjunctivally injected bevacizumab, etanercept, and the combination of both drugs on experimental corneal neovascularization

Cited by 27 publications

References 34 publications

Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study

Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study

Comparison of the effects of subconjunctival and topical anti-VEGF therapy (bevacizumab) on experimental corneal neovascularization

Tumor Necrosis Factor-α Inhibitors as a Treatment of Corneal Hemangiogenesis and Lymphangiogenesis

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