Effects of Conbercept in Refractory Uveitic Macular Edema and VEGF

Study Overview
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Brief Summary
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As a primary exploratory study, this study aims to evaluate the short-term effectiveness of intravitreal Conbercept injection in UME, and to explore the correlation between inflammatory factors like VEGF and the responsiveness to treatment.

Detailed Description
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Uveitic macular edema (UME) is one of the commonest and severest complications of chronic uveitis, and is also one of the important causes of permanent vision loss in uveitis. The pathophysiological mechanism of UME remains unclear, but was thought to be caused by damages of internal/external blood-retinal barrier mediated by inflammatory factors, including interleukin-2, interleukin-10, tumor necrosis factor α, prostaglandins and vascular endothelial growth factor (VEGF). Current treatments of UME include local or systemic glucocorticosteroids (GCS), immunosuppressants and biological agents. Although large dose of systemic GCS combined with immunosuppressants lead to quick resolution of ME in most of the cases, UME often relapse with tapering of GCS, and the side effects can be significant. Periocular or intraocular injection of GCS is effective in short term, but repetitive injections often lead to high intraocular pressure and cataract. Intravitreal injection of anti-VEGF agents is a huge advance of medical treatment in ophthalmology in recent years. Since 2007 till now, there have been a number of reports on the effectiveness of intraocular Bevacizumab and Ranibizumab injection in UME, but none about Conbercept. Besides, as the target of anti-VEGF agents, intraocular concentration of VEGF and its changes might be correlated to the sensitivity and responsiveness of UME to anti-VEGF agents, but has not been monitored. As a primary exploratory study, this study aims to evaluate the short-term effectiveness of intravitreal Conbercept injection in UME, and to explore the correlation between inflammatory factors like VEGF and the responsiveness to treatment.

Official Title
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Effectiveness of Conbercept in Treating Refractory Uveitic Macular Edema and the Changes of VEGF Levels in the Aqueous Humor

Conditions
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Uveitis, Macular Edema, Vascular Endothelial Growth Factor, Effect of Drugs

Intervention / Treatment
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* Drug: intravitreal injection of Conbercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >= 18 years old competent in signing the informed consent no severe systemic diseases unrelated to uveitis fulfill the criteria of refractory UME Exclusion Criteria: pregnant or preparing pregnancy already in other clinical trials blood pressure >= 180/110mmHg BCVA of the contralateral eye <= 20/200 cardiovascular events within 3 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: refractory UME patients treated with Conbercept<br>patients in this arm should meet the inclusion criteria and the definition of refractory UME | Drug: intravitreal injection of Conbercept<br>* patients will receive intravitreal injection of Conbercept, and at the same time, aqueous humor sample will be obtained from the anterior chamber to measure the concentrations of cytokines.<br>* Other names: Lumitin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of best corrected visual acuity (BCVA) | changes from baseline BCVA at 1, 2, 3, 4, 5, 6 months after injection (at each follow-up visit) | baseline and at 1, 2, 3, 4, 5, 6 months after injection | 
| Changes of central retinal thickness (CRT) | changes from baseline CRT at 1, 2, 3, 4, 5, 6 months after injection (at each follow-up visit) | baseline and at 1, 2, 3, 4, 5, 6 months after injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes of concentration of inflammatory cytokines | inflammatory cytokines include VEGF-A, VEGF-B, interleukin (IL)-2, interleukin-6, interleukin-8, interleukin-10, interleukin-12, tumor necrosis factor (TNF) α, monocyte chemotactic protein-1 and macrophage inflammatory protein-1 | before injection (baseline), 1 month after the first injection, at the end of the study (6 months) | 
| inflammatory status | changes from baseline flare and cells in the anterior chamber at 1, 2, 3, 4, 5, 6 months after injection | baseline and at 1, 2, 3, 4, 5, 6 months after injection | 
| side effects of the eye: increase of intraocular pressure | changes from baseline intraocular pressure at 1, 2, 3, 4, 5, 6 months after injection | baseline and at 1, 2, 3, 4, 5, 6 months after injection | 
| side effects of the eye: development/exacerbation of cataract | whether cataract is developed or exacerbated | baseline and at 1, 2, 3, 4, 5, 6 months after injection | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uveitis, Macular Edema, vascular endothelial growth factor, aqueous humor, Effect of Drugs