Retinal artery occlusion after facial filler injection in a patient with patent foramen ovale: a case report and literature review

Abstract

We describe a young woman with patent foramen ovale who developed multiple retinal artery occlusion in the right eye after injection of hyaluronic acid into the nasal root. She reported a gradual decline in visual acuity, with visual field defects that had developed in two stages. Multiple retinal artery occlusion was confirmed by slit-lamp examination, dilated fundus examination, optical coherence tomography, visual field examination, and fundus fluorescein angiography. A patent foramen ovale was detected by electrocardiography, transesophageal echocardiography, and transthoracic sonography. The patient was treated with intravenous dexamethasone and cobamamide, as well as extracorporeal counterpulsation therapy; this approach has not been described in previous literature regarding retinal artery occlusion. The patient’s visual acuity improved from counting fingers at 30 cm to 20/133 within 3 days. Our report emphasizes the need for better understanding of vascular anatomy to minimize the risk of complications. Moreover, patients undergoing hyaluronic acid injection should receive information regarding the potential for mild and severe complications; relevant tests should be performed before surgery to exclude vulnerable patients. Finally, a nursing system is needed to facilitate the emergency recognition, triage, and management of retinal artery occlusion.

Introduction

Hyaluronic acid (HA) facial filler injection, a type of minimally invasive surgery, is increasingly utilized worldwide to improve facial contours and lines.^1,2 Facial fillers can cause adverse reactions, but most reactions are mild. Although facial filler injection is safer and more easily controlled than conventional surgery, the emergence of this new method has led to increasing reports of serious adverse events, such as arterial obstruction-related vision loss, skin changes, muscle paralysis, and periorbital vascular lesions.^1,3–11 Thus far, no authoritative clinical guidelines have been established.

Retinal artery occlusion (RAO) is an acute ischemic stroke within the eye that can result in severe vision loss. RAO is rare in younger patients; only 11.4% of cases occur among individuals aged <50 years. ¹² Additionally, 67% of patients with RAO have at least one cardiovascular risk factor.^13,14 Current guidelines recommend excluding patent foramen ovale (PFO) and other sources of embolism in patients with suspected RAO. ¹⁵

PFO, a risk factor for ischemic thromboembolic events, is present in approximately 30% of healthy adults. Cardiogenic emboli can block the retinal artery by passing through an unsealed PFO and entering a specific blood flow pathway.^16,17 There have been multiple reports of PFO as a source of emboli in patients with RAO.^14,17–23

Here, we describe a young woman who developed multiple RAO in the right eye after HA injection into the nasal root. She had a concurrent PFO and experienced vision loss in two stages, leading to a gradual decline in visual acuity. Retrograde embolization of material from the nasal root into the retinal vasculature can occur through multiple anastomoses between the facial and orbital blood supplies.^1,5 Theoretically, emboli can enter the retinal artery through a PFO, leading to RAO. We performed extracorporeal counterpulsation therapy, which has not been described in previous literature regarding RAO; the patient's vision improved within 3 days.

Case presentation

A 40-year-old woman presented to our clinic with blurred vision in her right eye, accompanied by temporal and superior visual field obstruction, which had developed after HA injection as facial filler into the nasal root. She did not report any serious discomfort (e.g., eye pain, ocular swelling, or tearing), but she stated that the visual field defects had gradually developed after injection. She also noted that the superior and temporal visual field defects had not occurred simultaneously; the superior defect developed prior to the temporal defect. Furthermore, she experienced brief shortness of breath and the onset of visual symptoms after HA injection as facial filler.

A comprehensive and systematic examination of the patient revealed the following findings. She was alert, showed no signs of confusion, and had multiple dark red needle injection marks in the nasal root. Her nasal bridge was swollen, purple, and tender on palpation. There were no clinically significant signs in any other system. Her best-corrected visual acuity findings were counting fingers at 30 cm in the right eye and 20/20 in the left eye. Her intraocular pressure values were 17 mmHg in the right eye and 15 mmHg in the left eye. She had a swollen right eyelid, conjunctival congestion, transparent cornea, deep anterior chamber, round pupil (∼3 mm diameter), and sluggish light reflex. Both eyes displayed normal movement. Funduscopic examination and fundus photography (Figure 1) revealed a clear optic disc in the right eye, with a cherry-red spot in the macula that was suggestive of RAO. There were large areas of white edematous lesions along arterioles in the macular and temporal areas of the retina, along with evidence of transparent emboli and dot-like lesions in distant peripheral regions of the nasal and superior retina. Optical coherence tomography (Figure 2) revealed enhanced reflection in the retinal nerve fiber layer and thickening in the macula. Perimetry showed that the visual field defect in the right eye was mainly in the superior nasal quadrant; it extended horizontally beyond the midline. Fundus fluorescein angiography (Figure 3) demonstrated delayed filling of the temporal inferior artery, venous stasis, and larger areas of nonperfusion in the temporal retina (both superior and inferior regions). In all examinations, the left eye displayed no apparent abnormalities. Based on the findings in clinical examinations and imaging investigations, the patient was diagnosed with multiple RAO.

Figure 1.

Fundus examination revealed a clear optic disc margin in the right eye, with a cherry-red spot in the macular region (red arrow). Large fan-shaped white edematous lesions were visible in deep retinal layers below the macula and on the temporal side, with faintly visible transparent emboli (yellow arrow). Scattered lesions were also visible at the distal ends of the nasal and superior microvasculature.

Figure 2.

Optical coherence tomography assessment of the right eye showed increased reflectivity in the retinal nerve fiber layer and thickening in the macular area, along with diffuse thickening and hyperreflectivity in the inner retinal layers.

Figure 3.

Fundus fluorescein angiography revealed that the optic disc margin was clear. Large areas of nonperfusion were visible in the temporal and inferior retinal arteries.

During initial evaluation, the patient was given sublingual nitroglycerin (0.6 mg) and instructed to breathe regularly. She was then admitted to the hospital for emergency treatment. Upon admission, physical examination and electrocardiography revealed an altered T-wave and sinus arrhythmia. Transesophageal echocardiography and transthoracic sonography revealed mild mitral and tricuspid regurgitation, left ventricular filling abnormalities, and a PFO (Figure 4). Bilateral carotid ultrasound and brain magnetic resonance imaging findings were normal, and the results of blood tests were unremarkable. During hospitalization, the patient received intravenous dexamethasone (10 mg once daily) and intravenous cobamamide (500 µg once daily); she also underwent extracorporeal counterpulsation therapy (twice daily). After 3 days of treatment, an ophthalmic examination revealed fewer areas of white lesions around the optic disc, with visual acuity findings of 20/200 (corrected visual acuity: −1.75 diopter sphere/−1.75 diopter cylinder × 105° = 20/133) in the right eye and 20/20 in the left eye. During the 6-month follow-up period after discharge, visual acuity in the patient’s right eye did not substantially improve.

Figure 4.

Transesophageal echocardiography (a, b, c) and transthoracic sonography (d, e, f) revealed mild mitral and tricuspid regurgitation (b), left ventricular filling abnormalities (b), and a patent foramen ovale (a, red arrow). A small trans-septal shunt with a 13-mm-long gap was present in the central part of the interatrial septum. The gap was located between the primary and secondary septa; it had an overall surface width of 3.4 mm (1.4 mm on the right atrium and 2 mm on the left atrium) (c). Postoperative assessment revealed numerous microbubbles (d, e, f) with intense echoes in the left atrium.

Discussion

Visual impairment is a rare but very serious complication after HA injection as facial filler.^1,5,8 Vision loss and visual field defects after facial filler injection can be triggered by RAO, a disease involving retinal artery obstruction and the corresponding lack of retinal perfusion; these phenomena result in acute ischemia and hypoxia, intracellular edema, and rapid death of cells throughout the retina, ultimately leading to visual impairment. ¹⁴ Prompt and appropriate action is essential to preserve vision in an affected patient. ²⁴ Emergency treatment is intended to restore retinal perfusion within 90 minutes.^10,25 HA injection-related visual impairment typically occurs during the injection itself. ²⁶ The filler most commonly associated with visual impairment is HA ¹ : a dose of 0.08 mL can cause central retinal artery thrombosis. ²⁷ The symptoms in our patient appeared after HA injection as facial filler, which resulted in multiple RAO and a visible clot in the fundus.

PFO, the most common congenital heart disease in adults, involves a right-to-left atrial shunt. The incidence of PFO in the general population is approximately 30%. ¹⁷ Although most patients with PFO are asymptomatic, a PFO enables venous thrombi, air, fat, or infectious substances to bypass filtration within pulmonary capillaries and enter the systemic circulation, possibly causing an embolism. When a patient with PFO is at rest, right-to-left shunting generally does not occur; clinical symptoms appear when pressure is higher in the right heart than in the left heart, often because of a transient increase in pressure related to factors such as coughing, sneezing, or the Valsalva maneuver. Venous system emboli (e.g., thrombi or air emboli) return to the right heart through the venous system, then directly enter the left heart through the PFO (bypassing the pulmonary circulation) and flow into the systemic circulation, resulting in embolism onset at sites of vascular injury.^28,29 Our patient demonstrated a positive bubble test result, indicating that she had a PFO. Considering the presence of dyspnea and a possible right-to-left shunt, we could not rule out the contribution of the PFO to RAO onset.

Possible mechanisms underlying RAO onset

In most reported cases of visual impairment after HA injection as facial filler, injection was performed in a single location (generally at the nasal root),^5,8 consistent with injection method used in our patient. Other sites of facial filler injection associated with visual impairment include the forehead, glabella, temples, upper eyelid margin, eyebrows, and midface.^5,8 These regions receive blood supply either from the arteriolar network connected to the ophthalmic artery or from the facial artery, which is usually linked to branches of the ophthalmic artery. ³⁰ Blood flow to the eye travels from the internal carotid artery-ophthalmic artery to branches that supply intraocular structures (e.g., posterior ciliary and central retinal arteries) and extraocular muscles (e.g., dorsal nasal, supraorbital, and frontal arteries); these branches also supply nearby facial tissues and anastomose with branches of the external carotid artery.^1,27,30

The retrograde flow mechanism is the most widely accepted explanation for HA injection-related blockage.^5,7,31,32 Injection pressure exceeding systolic blood pressure, a sufficient volume of filler in the vessel lumen, and retrograde followed by anterograde flow of filler into the ocular circulation may result in vision loss after HA injection as facial filler. ³¹ This mechanism involves accidental injection of filler into ocular branches of the ophthalmic artery (supratrochlear, dorsal nasal, or supraorbital arteries) or into branches of the facial or temporal superficial arteries that communicate with the ophthalmic artery system. The high-pressure injection disrupts blood flow and pushes the filling material toward the main trunk of the ophthalmic artery. After injection, HA transport via blood flow leads to the blockage of various arteries that nourish the retina and optic nerve (e.g., central retinal and posterior ciliary arteries).^7,32 However, considering the rapid rate of arterial blood flow throughout the body, the theory of retrograde embolism from the dorsal nasal artery to the ophthalmic artery has been controversial. An animal experiment exploring the potential for retrograde embolism from the facial artery to the ophthalmic artery system showed that the probability of retrograde filler entry into the ophthalmic artery was much lower among live animals than among deceased animals. ³³ The findings in another study suggested that the pressure required for retrograde HA entry into an artery is substantially higher than the typical injection pressure generated by a syringe. ³⁴

After filler entry through the anastomotic branches of the ophthalmic artery, the presence and patency of those anastomotic branches strongly influence the potential for occlusion within the retinal artery or posterior ciliary arteries.^1,26,27,30 This hypothesis may also explain related symptoms: filler injection anywhere in the facial arterial region could cause ophthalmic artery occlusion.

Through the above two mechanisms, HA injection can cause immediate vision loss. ⁵ In our patient, transthoracic and transesophageal echocardiography confirmed the presence of a continuous right-to-left shunt. Considering that the patient's visual impairment occurred in two stages (rather than immediately after injection) and was accompanied by dyspnea after the injection, we speculate that the embolus entered the vein after HA injection into the nose. It subsequently traveled through the superior vena cava to reach the right heart, directly entered the left heart through the PFO, and then flowed into the systemic circulation through the internal carotid artery; ultimately, it caused branch RAO. The accumulation of additional cases involving PFO-related arterial obstruction may confirm this speculation. To prevent similar situations, we recommend performing PFO examination as an initial assessment prior to facial filler injection.

Treatment

Previous reports indicate that visual acuity rarely improves after facial filler injection-related vascular occlusion.^5,9 Treatment approaches vary; reported methods include intraocular pressure reduction, high-flow oxygen therapy, vasodilation, antiplatelet therapy, and hyaluronidase injection.^4,5,26,32,35 Drugs such as eye massage, anterior chamber paracentesis, mannitol, and acetazolamide can decrease intraocular pressure and increase retinal perfusion pressure. High-flow oxygen therapy can improve retinal oxygenation via choroidal diffusion to compensate for hypoperfusion within the central retinal artery system. Additionally, sublingual nitroglycerin 5 mg reduces vascular resistance and enhances perfusion.

Many clinicians recommend hyaluronidase injection as an emergency treatment.^1,32 However, the injection method, dose, and efficacy remain uncertain, particularly among patients who do not rapidly seek treatment.^{1,5,8,27,32,36} There is controversy concerning the efficacy and safety of thrombolysis treatment for RAO; large-scale, randomized, controlled phase III clinical trials are urgently needed to resolve this debate.

Our patient was treated with a relatively conservative method: extracorporeal counterpulsation therapy, a non-invasive external pulsation therapy introduced in China in the 1980s to manage angina pectoris. ³⁷ This method establishes new vessels and expands the vascular network around the obstructed coronary artery, thereby enhancing blood flow to the myocardium. As a mechanical method, counterpulsation reduces aortic systolic pressure and enhances aortic diastolic pressure; it can support cardiac function, improve blood circulation, and increase the perfusion of various organs (e.g., heart, brain, eyes, and kidneys). Extracorporeal counterpulsation therapy is non-invasive, has few side effects, and is easy to perform.

Outcome

Our therapeutic strategy had a moderate effect. After 3 days of treatment, the patient's visual acuity improved from counting fingers at 30 cm to 20/133 in the right eye; she was satisfied with this result. At discharge, there were fewer areas of white edematous lesions in the retina, which may have contributed to the improvement in visual acuity. However, the absorption of retinal edema within 3 days during the natural course of disease is unknown. Further studies are needed to determine the effectiveness of this treatment regimen, as well as its underlying mechanism.

Conclusion

To prevent similar situations, we recommend performing PFO examination as an initial assessment prior to facial filler injection. Additionally, extracorporeal counterpulsation therapy to enhance the retinal blood supply may be an effective treatment for HA injected-related RAO. This report emphasizes the need for a better understanding of vascular anatomy to minimize the risk of complications. Moreover, patients undergoing HA injection should receive information concerning the potential for mild and severe complications; relevant tests should be performed before surgery to exclude vulnerable patients (e.g., patients with PFO). A nursing system should be established to enable the emergency recognition, triage, and management of RAO. Further research is needed to evaluate long-term quality of life in patients with RAO, and population-based studies are warranted to elucidate the contemporary epidemiological characteristics of RAO. Future investigations should explore effective treatments for RAO with various etiologies; examples include novel thrombolytic drugs, extracorporeal counterpulsation therapy, hyperbaric oxygen therapy, and the use of neuroprotective agents during reperfusion therapy.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605231194514 - Supplemental material for Retinal artery occlusion after facial filler injection in a patient with patent foramen ovale: a case report and literature review

Supplemental material, sj-pdf-1-imr-10.1177_03000605231194514 for Retinal artery occlusion after facial filler injection in a patient with patent foramen ovale: a case report and literature review by Mingwei Si and Hong Wang in Journal of International Medical Research

Supplemental Material

sj-pdf-2-imr-10.1177_03000605231194514 - Supplemental material for Retinal artery occlusion after facial filler injection in a patient with patent foramen ovale: a case report and literature review

Supplemental material, sj-pdf-2-imr-10.1177_03000605231194514 for Retinal artery occlusion after facial filler injection in a patient with patent foramen ovale: a case report and literature review by Mingwei Si and Hong Wang in Journal of International Medical Research