Difference of Aqueous Cytokines According to Extent and Location of Ischemia Assessed by Ultra Wide Field Fluorescein Angiography in Macular Edema Secondary to Retinal Vein Occlusion by Min Sagong



To investigate the extent and location of nonperfusion area (NPA) associated with changes of aqueous cytokines in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) to analyze their association with best corrected visual acuity (BCVA) and macular thickness.


This prospective study included 30 patients with ME secondary to RVO and 10 age-matched control subjects. Angiopoietin-1, Angiopoietin-2, MCP-1, IL-8, IL-6, PDGF-AA, PlGF, and VEGF-A levels in the aqueous humor were measured before intravitreal injection or cataract surgery using suspension array technology. Baseline ultra-widefield fluorescein angiography (UWF FA) was used to quantify NPA and ISI defined as a ratio of NPA to total retina with stereographic projection method to correct peripheral distortion. To assess the amount and severity of NPA in different areas, concentric rings centered on the fovea were defined as five zones: peri-macular area (PMA, 0.5-3 mm radius), near-peripheral area (NPA, 3-10 mm), mid-peripheral area (MPA, 10-15 mm), far-peripheral area (FPA, 15 mm-normal perfusion boundary), and the peripheral normal avascular area. The levels of aqueous cytokines between RVO patients and control subjects were compared. And the association between NPA and ISI from the various rings/zones and BCVA, central macular thickness (CMT), and cytokines was evaluated in RVO patients.


The aqueous levels of MCP-1, IL-8, IL-6, PlGF, and VEGF-A were significantly higher in RVO group than control group. Total ISI showed a significant positive correlation with CMT and the concentrations of angiopoietin-1, angiopoietin-2, MCP-1, IL-8 PlGF, and VEGF-A. BCVA was significantly correlated with NPA and ISI only in PMA. All rings/zones except for FPA were significantly correlated with CMT and the levels of angiogenic cytokines like VEGF-A, PlGF, and angiopoietin-2. But the levels of inflammatory cytokines like MCP-1, IL-6, and IL-8 were significantly associated with NPA and MPA.


Angiogenic and inflammatory cytokines in aqueous humor were overexpressed in RVO patients and showed a distinct difference according to the location and extent of NPA. Increased levels of angiogenic cytokines were associated with NPA in the posterior and mid-peripheral area. Levels of inflammatory cytokines were increased in association with NPA in the mid-peripheral area.



Min Sagong, Donghyoun Noh, Gahyung Ryu, Junyeop Lee, Jano van Hemert
Yeungnam University College of Medicine
South Korea
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