Tear trough deformity is a popular target for the treatment with filler injections. The side effects are generally mild and transient. However, delayed complications may occur. We aim to perform a thorough systematic review of the published literature related to delayed complications after tear trough filler injections. A search of published literature was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in June 2021 and included PubMed, ScienceDirect, and Embase databases. The Medical Subject Headings (MeSH) terms used included the following terms: delayed complications, nodules, granulomas, swelling, discoloration, dermal filler, hyaluronic acid (HA), polyacrylamide, calcium hydroxyapatite (CaHA), poly-L-lactic acid (PLLA), eyelid, periorbital, periocular, and tear trough. Twenty-eight articles consisting of 52 individual cases were included in the final analysis. 98% (51/52) of patients were female and had an average age of 48.3 years. HA was the most reported product (71.2%, 37/52), followed by PLLA (4/52, 7.7%), and CaHA (4/52, 7.7%). The most common delayed complication with any dermal filler was swelling (42.3%, 22/52) followed by lumps or nodules (25.0%, 13/52). Xanthelasma-like reaction (17.3%, 9/52), migration (7.7%, 4/52), discoloration (3%, 3/52) also occurred. The average time of onset of any complication was 16.8 months with xanthelasma-like reaction appearing soonest (mean: 10 months) and discoloration appearing latest (mean: 52 months). Most swelling cases were caused by HA. Semi-permanent fillers such as PMMA and synthetic fillers such as PLLA were more likely to be associated with lumps and nodules than other complications. It is important that clinicians who perform tear trough augmentation with dermal fillers have a thorough understanding of the risks of the procedure to diagnose and manage them promptly as well as provide patients with accurate information regarding the potential adverse effects.

ABSTRACT:The most feared complication of the hyaluronic acid injections in the periorbital region is embolism of the central retinal artery. The present study aimed to compare the effectiveness of hyaluronidase administered intravenously (systemically) alone or in combination with streptokinase with that of intra-arterial revascularization. Thirty rats were divided into 5 groups. The bilateral oblique groin flap of the rats was raised; the right side was the experiment group, and the left side was the sham control. The right superficial epigastric artery was occluded with a hyaluronic acid injection. After occlusion, no additional procedures were performed in group 1, whereas group 2 received systemic hyaluronidase, group 3 received intra-arterial hyaluronidase, group 4 received systemic hyaluronidase and streptokinase, and group 5 received intra-arterial hyaluronidase and streptokinase. On the seventh day, the rats were killed, flap necrosis rate was calculated, and histological examination was performed. There was no significant difference in the necrosis rates of the rats in groups 2, 3, 4, and 5 (P > 0.05). In histological evaluation, the histological view closest to normal arterial structure was observed in group 4. Immunohistochemical analysis revealed that the ischemia scores of systemic therapy were significantly lower than those of intra-arterial therapy. These results have shown that hyaluronidase and streptokinase administered systemically is as effective as intra-arterial revascularization and does not cause arterial wall degeneration. It has been shown that systemic administration of hyaluronidase and streptokinase is as successful as intra-arterial revascularization in the treatment of arterial embolism with hyaluronic acid.

We present the first reported cases of delayed inflammatory reactions (DIR) to hyaluronic acid (HA) dermal fillers after exposure to the COVID-19 spike protein. DIR to HA is reported to occur in the different scenarios including: secondary to poor injection technique, following dental cleaning procedures, following bacterial/viral illness, and after vaccination. In this report of 4 cases with distinct clinical histories and presentations: one case occured following a community acquired COVID-19 infection, one case occured in a study subject in the mRNA-1273 clinical phase III trial, one case occurred following the first dose of publically available mRNA-1273 vaccine (Moderna, Cambridge MA), and the last case occurred after the second dose of BNT162b2 vaccine (Pfizer, New York, NY). Injectable HA dermal fillers are prevalent in aesthetic medicine for facial rejuvenation. Structural modifications in the crosslinking of HA fillers have enhanced the products' resistance to enzymatic breakdown and thus increased injected product longevity, however, have also led to a rise in DIR. Previous, DIR to HA dermal fillers can present clinically as edema with symptomatic and inflammatory erythematous papules and nodules. The mechanism of action for the delayed reaction to HA fillers is unknown and is likely to be multifactorial in nature. A potential mechanism of DIR to HA fillers in COVID-19 related cases is binding and blockade of angiotensin 2 converting enzyme receptors (ACE2), which are targeted by the SARS-CoV-2 virus spike protein to gain entry into the cell. Spike protein interaction with dermal ACE2 receptors favors a pro-inflammatory, loco-regional TH1 cascade, promoting a CD8+T cell mediated reaction to incipient granulomas, which previously formed around residual HA particles. Management to suppress the inflammatory response in the native COVID-19 case required high-dose corticosteroids (CS) to suppress inflammatory pathways, with concurrent ACE2 upregulation, along with high-dose intralesional hyaluronidase to dissolve the inciting HA filler. With regards to the two vaccine related cases; in the mRNA-1273 case, a low dose angiotensin converting enzyme inhibitor (ACE-I) was utilized for treatment, to reduce pro-inflammatory Angiotensin II. Whereas, in the BNT162b2 case the filler reaction was suppressed with oral corticosteroids. Regarding final disposition of the cases; the vaccine-related cases returned to baseline appearance within 3 days, whereas the native COVID-19 case continued to have migratory, evanescent, periorbital edema for weeks which ultimately subsided.

Injection of soft tissue fillers for esthetic purposes is considered a relatively simple, minimally invasive procedure. . We report a case of a 61 y/o male with an unusual case of foreign body granulomas arising on his forehead and periorbital region for the past 3 years. He had no drug allergies or history of trauma. He only recalled administration of "Botox" near the affected area 20 years ago, although he acknowledged being unsure of the nature of the substance. Examination showed bilateral, periorbital, edematous plaques, with subcutaneous nodules on the forehead. Punch biopsy showed multiple vacuoles surrounded by collagen bundles in the dermis, a histiocytic infiltrate, and multinucleated giant cells. Based on clinicopathological correlation, a diagnosis of foreign body granuloma related to silicone filler injections was made. He was treated with intralesional steroids and doxycycline 100 mg twice daily with complete resolution. Physicians should acknowledge this potential complication of silicone fillers and should inquire about their use with close-ended questions. We also review the diagnostic and therapeutic challenges faced by physicians when encountering this diagnosis.

The desire for longevity, beauty, and health is as old as the history of human culture. Minimizing tissue damage and invasive surgeries has led to a variety of options in the 21 century medicine. In the past 20 years, hyaluronic acid filler injections have thus become a popular modality of treatment for facial rejuvenation due to low costs for patients with immediately visible results. Ideally, the treated face looks natural. We aim at stopping time, maybe tweaking the handles of our clocks a bit backward to counteract aging processes, but creating a natural look and maintaining the individual appearance.

The soft-tissue composition of the eyelid varies from lateral to medial, in that the orbicularis area (in square millimeters) is greatest medially and least laterally, whereas the reverse is true for the preauricularis and postorbicularis fat. The purpose of this study was to describe the relative contribution of tissue types to the volume of the lower eyelid-midface junction. This is an observational cohort study of 11 subjects (20 eyes) without a history of orbital or periorbital surgery or abnormality. Quasi-sagittal surface coil magnetic resonance imaging scans in planes parallel to the long axis of each orbit were obtained during central gaze fixation. Measurements of the tissue area (in square millimeters) of the skin, preorbicularis fat, orbicularis, and postorbicularis fat were obtained in the center, medial, and lateral eyelid regions. Differences in tissue area across the eyelid were assessed. The segmental cross-sectional area and percentage of total segment represented by the orbicularis muscle increased from the lateral (9.4 mm; 21.8 percent) to the central (14.1 mm; 35.0 percent) and to the medial (18.5 mm; 47.0 percent) eyelid (p < 0.01). The inverse pattern was noted for both preorbicularis and postorbicularis fat, each occupying less area (in square millimeters) from lateral to medial (p < 0.01). Skin thickness did not vary significantly across the eyelid. The soft-tissue composition of the eyelid varies from lateral to medial in that the orbicularis increases in area, whereas the reverse is true for the preorbicularis and postorbicularis fat. This anatomical progression may help to explain the stereotypical location of blue discoloration in some patients after hyaluronic acid filler injection.

BACKGROUND:With the growth in the popularity of facial filler injections, increased numbers of severe adverse events, such as cerebral embolism, have been reported. OBJECTIVES:The aim of this article was to summarize the clinical manifestations and proposed mechanisms of filler-induced cerebral embolism (FICE). METHODS:A literature review was performed with the search keywords "filler injection," "hyaluronic acid," "fat graft," "cerebral infarction," "cerebral embolism," "stroke," "cerebrovascular infarction," "disorders of consciousness," and "hemiplegia." RESULTS:Among the 43 cases of FICE enrolled from 35 articles, 37 patients were female, and 6 were male. Twenty-nine of these patients had received fat grafting, and 12 hyaluronic acid injection. Most FICE patients had been injected in the glabella, followed by the temporal, forehead, and nasal areas. Among 30 patients injected under local anesthesia, 43.33% presented with neurologic symptoms during the procedure. The main symptoms were consciousness disorders and hemiplegia. Most of the embolization sites were in the middle cerebral artery, followed by frontal lobe infarction and anterior cerebral artery infarction. Three patients developed cerebral hemorrhage after embolism. Twenty-six patients presented with newly acquired vision loss. The management for FICE cases included embolectomy, thrombolysis, decompressive craniectomy, antiplatelet/anticoagulant therapy, and symptomatic and nutritional treatment. Nearly half of the patients recovered or exhibited improved neurologic manifestations but not visual loss. Five patients died. CONCLUSIONS:FICE is a severe complication following facial filler injection. Careful prevention, timely identification, and treatment are crucial to decreasing the morbidity and mortality of FICE. LEVEL OF EVIDENCE: 4: