The efficacy of systemic and intravitreal infliximab treatments in an endotoxin-induced uveitis model

Dönmez, Oya; Yaman, Aylın; Öztürk, Taylan; Aktaş, Safiye; Altun, Zekiye; Yılmaz, Osman

doi:10.1080/15569527.2019.1632883

Cited by 6 publications

(6 citation statements)

References 48 publications

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“…18 Moreover, several clinical studies have re-ported intraocular inflammation after intravitreal injections of infliximab in nonuveitic patients, with doses as low as 0.5 mg, in 15% to 100% of patients. [11][12][13] Donmez et al 20 reported a paradoxical effect after intravitreal infliximab treatments in an experimental endotoxin-induced uveitis model. 20 Similarly, our study is the first clinical study to experience this paradoxical intraocular inflammation after intravitreal infliximab in uveitic patients.…”

Section: The Failed With Exacerbated Inflammation Eyesmentioning

confidence: 99%

Monthly Intravitreal Infliximab in Behçet's Disease Active Posterior Uveitis

Refaat

Abdullatif

Hamza

et al. 2021

Retina

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Purpose: To study the safety of extended monthly intravitreal infliximab injections in patients with active posterior uveitis in Behcet's disease.Methods: This is a prospective, interventional, noncomparative, open-label, pilot study of 9 monthly intravitreal infliximab injections (1 mg/0.05 mL) for 22 eyes of 16 patients with active posterior uveitis in Behcet's disease. Control of inflammation and visual outcomes were assessed, and ocular complications were monitored during the study period.Results: Successful treatment was achieved in 7 eyes (35%), and failure was encountered in 13 eyes (65%). Only seven eyes of six patients (35%) had completed the study and achieved complete resolution of inflammation with improved best-corrected visual acuity and no complications. Failure was either because of inability to control the inflammation in nine eyes (45%) or development of exacerbation of inflammation in four eyes (20%). Four eyes developed severe immunological reaction from the drug after first (n = 1), second (n = 2), and third (n = 1) injections and had to discontinue the injections. Kaplan-Meier survival analysis showed that the mean estimated time to failure was 3.3 ± 0.2 months, and all failed eyes required revision of their systemic immunotherapy to control the ocular inflammation.Conclusion: Intravitreal infliximab for active posterior uveitis in Behcet's disease was associated with a high complication rate and failure to control inflammation in most eyes. It should not be considered a substitute to systemic therapy.

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Section: The Failed With Exacerbated Inflammation Eyesmentioning

confidence: 99%

Monthly Intravitreal Infliximab in Behçet's Disease Active Posterior Uveitis

Refaat

Abdullatif

Hamza

et al. 2021

Retina

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“…A local administration of IFN alpha-2b to a rabbit model significantly decreased intraocular inflammation, particularly in the vitreous 74 . Although efficient treatment of NIU was reported in humans after intravitreal IFX injections 64 , 75 , 76 , these results could only be partly reproduced in animal studies 77 , 78 , 79 , 80 . Another recent study has used hydrogel eye drops as a carrier of ADA.…”

Section: Discussionmentioning

confidence: 91%

The Challenge of Treating the Severest Forms of Chronic Noninfectious Posterior and Panuveitis

Spartalis

Stübiger

Spitzer

et al. 2023

Klin Monbl Augenheilkd

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Background Noninfectious posterior and panuveitis may exhibit a chronic relapsing clinical course and are challenging to treat. Most affected patients are continuously treated with systemic immunosuppressive therapy, which is potentially associated with significant adverse side effects. Methods A cohort of 18 patients presenting with severe noninfectious posterior or panuveitis were evaluated with respect to the clinical course of the disease, with particular focus on best-corrected visual acuity (BCVA), treatment duration, remission rates, reported negative side effects, and the necessity for switching medication. Results The mean follow-up was 27.8 months. Although BCVA improved significantly, complete or partial remission was observed in only 66.7% of patients. Of the patients, 72.2% underwent a change in medical treatment due to either adverse events or inefficacy of medication. Conclusion Despite new immunosuppressive therapies, effective treatment of severe noninfectious posterior and panuveitis remains a major challenge. We discuss the urgent need for novel treatment strategies in order to prevent systemic adverse effects, and to improve visual outcome and quality of life.

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“…TNF-α levels are significantly elevated in the aqueous humor in the early stages of endotoxin-induced anterior uveitis [46,47]. Furthermore, the concentration of proinflammatory cytokines in the aqueous humor has been shown to increase before apparent clinical signs of anterior uveitis emerge; moreover, blocking signaling results in a significant delay in the onset of anterior uveitis pathologies [48,49]. Other studies have also assessed the effects of TNF-α on vascular leakage, leukocyte adhesion, and the recruitment of circulating inflammatory factors in ocular tissues [50,51].…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

et al. 2021

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Inflammation and oxidative stress are closely related processes in the pathogenesis of various ocular diseases. Uveitis is a disorder of the uvea and ocular tissues that causes extreme pain, decreases visual acuity, and can eventually lead to blindness. The pharmacological functions of fucoxanthin, isolated from brown algae, induce a variety of therapeutic effects such as oxidative stress reduction and repression of inflammation reactions. However, the specific anti-inflammatory effects of fucoxanthin on pathogen-associated molecular pattern (PAMP) lipopolysaccharide-induced uveitis have yet to be extensively described. Therefore, the aim of present study was to investigate the anti-inflammatory effects of fucoxanthin on uveitis in rats. The results showed that fucoxanthin effectively enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in ocular tissues. Furthermore, fucoxanthin significantly increased the ocular activities of superoxide dismutase and decreased the levels of malondialdehyde stimulated by PAMP-induced uveitis. Ocular hypertension and the levels of inflammatory cells and proinflammatory cytokine tumor necrosis factor-alpha in the aqueous humor were alleviated with fucoxanthin treatment. Consequently, compared to the observed effects in lipopolysaccharide groups, fucoxanthin treatment significantly preserved iris sphincter innervation and pupillary function. Additionally, PAMP-induced corneal endothelial disruption was significantly inhibited by fucoxanthin treatment. Overall, these findings suggest that fucoxanthin may protect against inflammation from PAMP-induced uveitis by promoting the Nrf2 pathway and inhibiting oxidative stress.

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The efficacy of systemic and intravitreal infliximab treatments in an endotoxin-induced uveitis model

Cited by 6 publications

References 48 publications

Monthly Intravitreal Infliximab in Behçet's Disease Active Posterior Uveitis

Monthly Intravitreal Infliximab in Behçet's Disease Active Posterior Uveitis

The Challenge of Treating the Severest Forms of Chronic Noninfectious Posterior and Panuveitis

Protective Effects of Fucoxanthin Dampen Pathogen-Associated Molecular Pattern (PAMP) Lipopolysaccharide-Induced Inflammatory Action and Elevated Intraocular Pressure by Activating Nrf2 Signaling and Generating Reactive Oxygen Species

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