Nonhuman Primate Model of Super-selective Intra-arterial Ophthalmic Arterial Interventional Thrombolysis for Treatment of Ophthalmic Arterial Embolism Resulting From Hyaluronic Acid Filler Cosmetic Injection.

Abstract

Although intravascular interventional thrombolysis therapy is beneficial for patients suffering from impaired vision caused by hyaluronic acid (HA) embolism, there is no medical evidence-base for the efficacy of this treatment. The aim of this study was to show that intra-arterial thrombolysis therapy (IATT) can effectively improve visual function after impairment caused by facial injection of HA within a certain time window, and to propose a clinically relevant model of retinal ischemia and reperfusion in nonhuman primates. Ophthalmic artery (OA) embolization in rhesus monkeys was induced by injecting HA into the OA, and reperfusion was achieved by IATT with hyaluronidase immediately and at 1, 4, and 24 hours after embolization. Digital subtraction angiography and fundus fluorescein angiography were used to evaluate blood flow before and after retinal reperfusion. Retinal structure and function before and after reperfusion were evaluated by electroretinography, hematoxylin and eosin staining, and transmission electron microscopy. scRNA-seq and bioinformatics analyses were used to detect retinal changes. Angiography confirmed complete ophthalmic arterial embolization after intra-arterial HA injection, and reperfusion after IATT with hyaluronidase. Electroretinography indicated retinal dysfunction following ischemia and recanalization, and it was found that recanalization of the OA at 1, 4, or even 24 hours could improve the visual function of the embolized eye, but some impairment of visual function was nevertheless observed. Histological damage in the retinal cells occurred postembolization. Single-cell sequencing indicated that rhodopsin cytokine expression decreased with longer embolization times. The monkey model presented in this study closely simulated retinal blood flow during OA ischemia and reperfusion in clinical practice and could help elucidate the molecular mechanisms underlying the visual impairment caused by retinal tissue cell ischemia.