Background <p>With increased dermal filler use, hyaluronic acid (HA) injection-induced blindness reports emerge. The underlying mechanism of HA-induced ophthalmic artery occlusion (OAO)-associated blindness and effective treatment modalities are currently unknown, primarily due to the lack of an ideal HA embolization blindness animal model.</p> Objective <p>In this study, we aimed to establish a feasible and reproducible animal model of OAO-induced blindness using interventional, ophthalmological, and behavioral approaches, thereby serving as an ideal preclinical model for research aimed at developing treatments for blindness induced by hyaluronic acid injection.</p> Methods <p>We injected HA into the porcine ophthalmic artery (OA) to induce retinal artery ischemia, assessing blood flow and intraretinal structures using digital angiography and ophthalmologic examination, and vision using the obstacle course test. We performed hematoxylin and eosin staining to observe the retina structure two months after embolization.</p> Results <p>Compared with normal baseline observations, post-embolization angiography suggested no OA visualization, fundus photography revealing a pale fundus and optic disk edema. Obstacle course collisions and completion times were significantly lower in the post-embolization OX (blindfolded right eye) than in the post-embolization XX (both eyes blindfolded) group, higher in the post-embolization OO (no blindfolded) than in the preoperative OO group, and lower in the pre-embolization OO than in the pre-embolization XX group. Compared with control eyes, the hematoxylin and eosin staining demonstrated a disordered retinal structural arrangement, a lack of retinal ganglion cells, and severe fibrosis in the experimental eyes.</p> Conclusion <p>In conclusion, we created a reproducible OAO blindness porcine model, which could serve as an ideal preclinical animal model for research on treatment strategies for patients with HA injection-induced blindness.</p> No Level Assigned <p>This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors<a href="http://www.springer.com/00266">www.springer.com/00266</a></p>