Abstract
Purpose:
Idiopathic epiretinal membranes (ERMs) are a common source of compromised vision in our aging population, prompting exploration for non-surgical approaches for the treatment of these patients. Vision loss in patients with ERMs is attributed to the development of macular edema (ME). Fluorescein angiography studies on patients with ERMs often demonstrate perifoveal vascular leakage, suggesting that hyperpermeability factors may promote ME in these patients. Indeed, immunohistochemical studies have demonstrated expression of hypoxia-inducible factor (HIF)-1α and its target, vascular endothelial growth factor (VEGF), in idiopathic ERMs supporting a role for VEGF and other (HIF-regulated) hyperpermeability factors in the promotion of ME in ERM patients. These data have encouraged clinicians to extend the use of “anti-VEGF” therapies, steroids and NSAIDs to patients with ERMs and ME. Here we assess the contribution of HIF-regulated hyperpermeability factors to the development of ME in patients with idiopathic ERMs.
Methods:
Johns Hopkins School of Medicine Institutional Review Board approval was obtained to collect vitreous samples from patients undergoing vitrectomy surgery. Concentrations of VEGF, angiopoietin 2 (ANGPT2), and angiopoitin-like 4 (ANGPTL4) were determined by ELISA and correlated with central foveal thickness (CFT) on OCT. Mann-Whitney U test and Spearman correlation statistical models were used to compare protein concentrations and to identify factors that independently correlate with idiopathic ERMs with ME.
Results:
Concentrations (n, mean +/- SD) of VEGF (29, 9.1 +/- 4.5 pg/mL), ANGPT2 (18, 101.7 +/- 34.9 pg/mL), and ANGPTL4 (29, 5.5 +/- 8.9 ng/mL) were not significantly higher in ERM patients compared to controls (24, 7.9 +/- 0.2 pg/mL; 12, 79.6 +/- 22.2 pg/mL; and 24, 4.6 +/- 5.2 ng/mL, respectively) and were markedly lower than those detected in patients with ischemic retinal disease. Levels of these hyperpermeability factors did not correlate with CFT.
Conclusions:
We demonstrate that the expression of hyperpermeability factors in the vitreous of patients with idiopathic ERMs is extremely low and similar to control patients. Our results suggest that the efficacy of therapies targeting these secreted factors may be limited for the treatment of ME in patients with idiopathic ERMs.