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

Abstract

Background: Although intravascular interventional thrombolytic therapy is beneficial to patients suffering from impaired vision induced by hyaluronic acid (HA) embolism, there is no evidence-based medical evidence. In this study, we put forth a clinically relevant model of retinal ischemia and reperfusion in nonhuman primates and generate a retinal cell atlas of ischemia injury.

Objectives: Evidence-based medicine proved that IATT can effectively improve the visual function of patients with visual impairment caused by facial injection of hyaluronic acid within a certain time window.

Methods: Ophthalmic artery (OA) embolization in rhesus monkeys was induced by injecting hyaluronic acid(HA) into the ophthalmic artery, and reperfusion was achieved by intra-arterial thrombolysis therapy (IATT) with hyaluronidase immediately and at 1h, 4h, and 24h after embolization. Digital subtraction angiography (DSA) and fundus fluorescein angiography (FFA) were used to evaluate blood flow before and after retina reperfusion. Retinal structure and function before and after reperfusion were evaluated using electroretinography (ERG), hematoxylin and eosin (HE) staining, and transmission electron microscopy (TEM). scRNA-seq and bioinformatics analyses were used to detect retinal changes during different reperfusion window of opportunity.

Results: DSA and FFA images confirmed ophthalmic arterial embolization completely after intra-arterial HA injection, and reperfusion after hyaluronidase-induced thrombolysis. ERG indicated retinal dysfunction following ischemia and recanalization exactly, and it was found that rcanalized the ophthalmic artery at 1 h, 4 h, or even 24 h could improve the visual function of the embolized eye, but immediately after recanalization to the 29th day after recanalization, the visual function of embolization time point in all three groups decreased to a certain extent. HE staining and TEM revealed ischemia-induced histological damage in the retina cells at different embolization time points. After single cell sequencing, it was found that the expression of RHO cytokines decreased with the extension of embolization time in reperfusion after 1 h,4h,6h of embolization.

Conclusions: The rhesus monkey model of ophthalmic artery ischemia and reperfusion presented in this study closely simulated retina blood flow during ophthalmic artery ischemia and reperfusion in clinical practice and could help elucidate the molecular mechanisms underlying the visual impairment caused by retina tissue cells ischemia.