Comparison of cytokine levels from undiluted vitreous of untreated patients with retinal vein occlusion

Abstract

ABSTRACT.Purpose: To compare cytokines in undiluted vitreous of treatment-naı¨ve patients with macular oedema without vitreomacular traction secondary to branch (BRVO), central (CRVO) and hemi-central (H-CRVO) retinal vein occlusion. Methods: Ninety-four patients (median age 72 years, 42 men) underwent an intravitreal combination therapy, including a single-site 23-gauge core vitrectomy and the application of bevacizumab and dexamethasone due to vision-decreasing macular oedema. Among these were 43 patients with BRVO, 35 with CRVO and 16 patients with hemi-CRVO, which were distributed in a fresh or old retinal vein occlusion type (seven or more months after onset). Undiluted vitreous samples were analysed for interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF-A) with cytometric BEAD assay. Vitreous samples from patients with idiopathic epiretinal membrane served as controls (n = 14). Results: The mean cytokine values were highest in the CRVO group with IL-6 = 64.7 pg ⁄ ml (SD ± 115.8), MCP-1 = 1015.8 pg ⁄ ml (±970.1) and VEGF-A = 278.4 pg ⁄ ml (±512.8), followed by the H-CRVO group with IL-6 = 59.9 pg ⁄ ml (SD ± 97.5), MCP-1 = 938.8 pg ⁄ ml (±561.1) and VEGF-A = 211.5 pg ⁄ ml (±232.4). The BRVO group had IL-6 = 23.2 pg ⁄ ml (SD ± 48.8), MCP-1 = 602.6 pg ⁄ ml (±490.3) and VEGF-A = 161.8 pg ⁄ ml (±314.4). The values of MCP-1 and VEGF-A were significantly different for CRVO or H-CRVO versus BRVO. All values were significantly higher than in the control samples, which had 6.2 ± 3.4 pg ⁄ ml (IL-6), 253 ± 74 pg ⁄ ml (MCP-1) and 7 ± 4.9 pg ⁄ ml (VEGF-A). Within the old RVO type, only MCP-1 was significantly different for CRVO or H-CRVO versus BRVO. Conclusions: Both inflammatory markers and VEGF-A were higher in CRVO and H-CRVO than in BRVO undiluted vitreous samples. It seems that monocyte recruitment to the vessel wall, which might underlie the importance of eosinophils in tissue remodelling after RVO, is of special interest owing to the significant difference in MCP-1 in the older RVO types.Key words: cytometric bead array -interleukin 6 -monocyte chemoattractant protein -retinal vein occlusion -vascular endothelial growth factor -vitreous samples Acta Ophthalmol. 2012: 90: e98-e103

Intravitreal Functional Plasminogen in Eyes with Branch Retinal Vein Occlusion

“…4); to the best of our knowledge, this has not been investigated before. In concordance with previously detected significant differences in intravitreal VEGF levels in eyes with CRVO and BRVO [12], lower plasminogen activities were expected in BRVO-affected eyes. The comparison of the data provided here of intravitreal functional plasminogen of 1.35 ± 1.11%N with previously reported plasminogen values of 2.19 ± 1.89%N in CRVO-affected eyes [11] supports our hypothesis.…”

“…It was recently demonstrated that functional plasminogen is significantly elevated in eyes with central retinal vein occlusion (CRVO) [11]. Intravitreal plasminogen activities in eyes suffering from BRVO were expected to be lower in comparison with CRVO-affected eyes in accordance with previously reported significantly different intravitreal VEGF levels in both retinal vein occlusion entities [12]. Thus the intravitreal detection of plasminogen in eyes with BRVO would provide new information about the pathophysiological processes after the acute event, because CRVO and BRVO are two distinct disease entities [13].…”

Intravitreal Functional Plasminogen Is Elevated in Central Retinal Vein Occlusion

“…No adverse events or serious side effects occurred and sampling vitreous fluids with either technique was revealed to be a safe procedure. Previous studies confirm those observations [12,13,14] although serious complications may occur and sampling aqueous humor was declared as a safer way to collect intraocular specimens [15,16]. Nevertheless, we decided to analyze vitreous samples instead of aqueous humor samples because intraocular plasminogen activity within the eye is low [17] and there is a substantial dilution effect between the anterior and posterior segments of the eye [11,18,19].…”

Vascular Endothelial Growth Factor (VEGF), Mast Cells and Inflammation

“…The aqueous levels ofVEGF and IL-6 are correlated significantly with the severity of macular edema. These observations suggest that VEGF and IL-6 are produced together in the intraocular tissues and are involved in the pathogenesis of macular edema (82)(83)(84)(85)(86). Recently, it was found that a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), is effective in treating ocular neovascularization.…”