Dmitriev PM, Wang H, Rosenblum JS, et al. - Researchers undertook this clinical case series with a transgenic murine model study, to report the ocular lesions in EPAS1 gain-of-function mutation syndrome as well as to ascertain if early-onset diminished visual acuity is developmental or related to long-term physiologic sequelae of the syndrome. Participants included 3 patients who were referred to the National Institutes of Health for assessment of recurrent and metastatic paragangliomas or pheochromocytomas accompanied by polycythemia. This analysis involved 3 patients (mean [SD] age, 29 [6.2] years) with established ocular abnormalities. A role of hypoxia-inducible factor 2α and hypoxia signaling in vessel development within the choroid and retina was revealed, suggesting that the persistence of venous elements within the developing mesenchyme was indicated by the marked permanent choroidal thickening and tortuous and dilated veins observed in the choroid and retina in patients with EPAS1 gain-of-function mutation syndrome. These revelations may explain other eye and vascular anomalies whose pathogenesis continues to be unclear.