PURPOSE: To investigate relationships among vitreous fluid levels of soluble vascular endothelial growth factor receptor-2 (sVEGFR-2), vascular endothelial growth factor (VEGF), and soluble intercellular adhesion molecule 1 (sICAM-1) in patients with branch retinal vein occlusion (BRVO) and macular edema or patients with idiopathic macular hole. DESIGN: Retrospective case-control study. METHODS: SETTING: Tokyo Women's Medical University and Eguchi Eye Hospital. PATIENT POPULATION: Forty-nine Japanese patients who underwent unilateral vitrectomy (27 with BRVO and 22 with macular hole). OBSERVATION PROCEDURES: Vitreous fluid samples were obtained during vitreoretinal surgery to measure the levels of sVEGFR-2, VEGF, and sICAM-1. Retinal ischemia was evaluated from capillary nonperfusion on fluorescein angiography. Macular edema was examined by optical coherence tomography. MAIN OUTCOME MEASURES: Vitreous fluid levels of the 3 molecules and severity of macular edema. RESULTS: BRVO patients had a significantly higher vitreous fluid level of sVEGFR-2 (median, 1670 pg/mL; interquartile range [IQL], 1205 to 2225 pg/mL) than macular hole patients (median, 1265 pg/mL; IQR, 731 to 1800 pg/mL; P = .017), as was the case for VEGF (median, 237 pg/mL; IQR, 42.2 to 1305 pg/mL; vs median, 15.6 pg/mL; IQR, 15.6 to 15.6 pg/mL; P < .001) and sICAM-1 (median, 10.1 ng/mL; IQR, 6.3 to 22.5 ng/mL; vs median, 4.1 ng/mL; IQR, 3.3 to 6.0 ng/mL; P < .001). In BRVO patients, there was a significant positive correlation between vitreous fluid levels of sVEGFR-2 or VEGF and sICAM-1, but not between sVEGFR-2 and VEGF. Vitreous fluid levels of all 3 molecules were correlated significantly the with severity of macular edema in BRVO patients. CONCLUSIONS: sVEGFR-2 may induce an increase of vascular permeability together with or via sICAM-1, or both with and via sICAM-1, in BRVO patients with macular edema. (Am J Ophthalmol 2011;152:669-677. (C) 2011 by Elsevier Inc. All rights reserved.)