1. Nonallergic Eyelid Edema After Botulinum Toxin Type A Injection Case Report and Review of Literature Chao-Ming Wu 1, Yin-Shuo Chang 1, 2, Chang-Cheng Chang 1, 3, Jen-Hsiang Shen 1, 4, Yu-Tsung Chen 5 1 Aesthetic Medicine Center, Department of Plastic Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan 2 Department of Medical Education, MacKay Memorial Hospital, Taipei City, Taiwan 3 Department of Cosmetic Science, Chang Gung University of Science and Technology, Taoyuan, Taiwan 4 Department of Medical Education, Tzu-Chi General Hospital, New Taipei City, Taiwan 5 Department of Dermatology, Taipei Municipal Wang Fan Hospital, Taipei City, Taiwan ** Nothing to disclose ** 2015 ASPS

2. Introduction Botulinum neurotoxin type A (BoNTA) 0 Aesthetic medicine as treatment for glabellar lines 0 Reduce muscle activities, decrease muscle tension, smooth facial wrinkles Ascher B, et al. J Eur Acad Dermatol Venereol. 2010;24:1278–1284 Ascher B, et al. J Eur Acad Dermatol Venereol. 2010;24:1285–1295 0 Adverse events after BoNTA injection: only 3.73% Kim BW, et al. J Dermatolog Treat. 2014;25:331–336 2

3. 0 Most adverse events: minor and transient, and composed of eye disfiguration and vision blockage 0 No consensus on incidence of adverse effects 0 Ptosis: frequent side effect, eyelid edema uncommon Kim BW, et al. J Dermatolog Treat. 2014;25:331–336 0 Few studies etiology, clinical course, and treatment outcomes 3

4. CASE REPORT 0 59-year-old woman 0 History of well-controlled asthma 0 BoNTA therapy to smooth wrinkles: forehead, glabella, corners of her eyes (crow’s feet) Physical examination revealed thick, triangular-shaped eyelids with infolding of the upper eyelid 0 BoNTA (BOTOX1, Allergan, Inc, Irvine, CA, 100 U in 4mL normal saline) 0 Forehead, glabella (12.5 U), and eye corners (12.5/12.5 U) 4

5. 0 Local allergic reaction to BoNTA 3-day follow-up 0 Painless, nonpruritic, bilateral periorbital swelling and erythema 0 A topical corticosteroid BID x 3days No symptom relief 0 Hypothesis: impaired venous and lymphatic return by reduced muscle tone rather than allergic / infection 0 Hot pads, blink frequently, and massage Eventually resolved 2 weeks later 5

6. 0 At 4-month follow-up, an additional course 0 Blink frequently, especially in the early morning 0 Massage the periorbital area  increase venous return No adverse effects and satisfactory outcome 6

7. DISCUSSION 0 Most common complications: bruising, dry eye, corneal exposure, diplopia, ectropion, lid retraction, other lid malpositions, and an asymmetrical smile Klein AW. Dermatol Clin. 2004;22:197–205. 0 Little known about periorbital eyelid edema: 0.04% Kim BW, et al. J Dermatolog Treat. 2014;25:331–336 0 Median onset time of eyelid edema: 5 0 Median duration: 15 days 0 Asian populations at greater risk than Caucasian Brin MF, et al. J Am Acad Dermatol. 2009;61: 961–970. 7

8. 0 Eyelid edema: allergy, infection, trauma, poor venous or lymphatic return 0 Procedural and possibly even local adverse effects 0 Related to injector experience, decline with cycles 0 Repeated treatments: lower incidence of eyelid ptosis, eyelid sensory disorder, and eyelid edema Brin MF, et al. J Am Acad Dermatol. 2009;61: 961–970 8

9. 0 Multiple muscles involved in the blinking reflex. 0 Levator palpebrae superioris, Mu ̈ller’s (superior tarsal) muscle 0 Pretarsal and posttarsal plexuses: venous drainage of eyelid 0 Ophthalmic vein: drain the forehead and temple. 0 Preauricular and parotid nodes: lateral segment, Submandibular: medial side Paul RE JP. 17th ed: McGraw Hill Professional; 2007. 9

10. 0 Local spread of toxin  Eyelid edema 0 Propose the mechanism: 0 Venous or lymphatic stasis, Decreased muscle tone 0 Different from ptosis Brin MF, et al. J Am Acad Dermatol. 2009;61: 961–970 0 Impaired mechanical venous return: more common in Asians than Caucasians Brin MF, et al. J Am Acad Dermatol. 2009;61: 961–970 0 Fewer fibrous attachments Kikkawa DO. Int Ophthalmol Clin. 1997;37:193–204. Nguyen MQ. Semin Plast Surg. 2009;23:185–197. 10

11. 0 Fusion of levator aponeurosis and orbital septum 0 Closer to eyelid margin  puffiness in Asian Nguyen MQ. Semin Plast Surg. 2009;23:185–197 Jeong S, et al. Arch Ophthalmol. 1999;117:907–912. Puffiness compresses the vein and obstructs venous return 11

12. 0 Asian eyes: eyelid hooding (dermatochalasis) 0  elastic fibers and  breakdown of collagen networks  Secondary lymphostasis and eyelid edema Nagi KS. Ophthalmology. 2011;118:1205–1210. 0 Examination of function and tone 0 Orbicularis oculi and levator palpebrae superioris muscles 12

13. 0 Doses and injection points in patients at risk 13

14. CONCLUSION 0 Periorbital edema: Rare, Self-limiting, ✖ medical treatment 0 Hot pads, frequent blinking, self-massage for venous return 0 Preventive strategies: Examination of orbicularis oculi and levator palpebrae superioris 0 Patients at risk: Asian, dermatochalasis, and poor periocular muscle tone  half dosage 14