Purpose: To investigate whether macular edema (ME) due to branch retinal vein occlusion (BRVO) associates with retinal overexpression of angiopoietin-like 4 (ANGPTL4). The aqueous ANGPTL4 and vascular endothelial growth factor (VEGF) levels in patients with ME due to BRVO were measured, and the relationships between ANGPTL4 levels and the degree of retinal ischemia and edema were determined.

Methods: The study and control groups consisted of all consecutive patients who were scheduled to undergo intravitreal bevacizumab injection for treatment-naïve BRVO with ME and senile cataract surgery, respectively. The study group was divided into the major BRVO and macular BRVO subgroups on the basis of the involved retinal area. The aqueous ANGPTL4 and VEGF levels were measured by enzyme-linked immunosorbent assay. In the patients with BRVO, capillary nonperfusion area by fluorescein angiography and central subfield macular thickness (CSMT) and total macular volume (TMV) by spectral-domain optical coherence tomography were determined.

Results: Patients with ME due to BRVO (50 eyes) had higher aqueous ANGPTL4 and VEGF levels than the controls (61 eyes)(both P< 0.001). The major BRVO had higher ANGPTL4 and VEGF levels than the macular BRVO (both P< 0.001). The aqueous ANGPTL4 levels of all BRVO patients correlated positively with nonperfusion area (r= 0.901, P< 0.001), CSMT (r= 0.574, P< 0.001), and TMV (r= 0.453, P= 0.001), even after adjustment for VEGF levels.

Conclusions: The aqueous ANGPTL4 levels correlated significantly with phenotypes of BRVO with ME. This suggests that ANGPTL4 may be a candidate biomarker and treatment target in ischemia-induced retinopathies, including BRVO.