Journal of Cosmetic and Laser Therapy, 2014; 16: 32–36


Rejuvenation effects of hyaluronic acid injection on nasojugal groove: Prospective randomized split face clinical controlled study

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of Dermatology, School of Medicine, Kyung-Hee University, Seoul, Republic of Korea and Nara Dermatologic Clinic, Seoul, Republic of Korea

Abstract Background: Pronounced nasojugal groove (tear trough deformity) is one of the landmarks of aging. Hyaluronic acid filler can be used for attenuating the nasojugal sulcus but irregular lumpness and overcorrection are common adverse reactions. Objectives: We evaluated the effect of Restylane Vital® with its specialized injector on volume correction and skin tone of nasojugal groove. Subjects and method: Ten Korean women were enrolled in this study. Subjects were randomized to be injected a stabilized hyaluronic acid-based gel of nonanimal origin (NAHSA injector, Restylane Vital®, Q-med) on one side of nasojugal groove, with the other side paired as control. The treatment was performed in one session. Outcome assessments included standardized photography, mexameter, and spectrometer for skin tone, global evaluation by blinded investigators, and patients’ self-assessment. An assessment was made before treatment, immediately after treatment, and 1, 3, and 6 months after the treatment. Results: All patients reported a high degree of satisfaction. Duration of overall effect varied among the patients. Correction of the nasojugal groove with a Restylane Vital® injector causes minimal tissue trauma and allows exact placement of hyaluronic acid. Restylane Vital® injector offers more predictable results and a lower incidence of adverse effects than more commonly used techniques. Conclusions: Hyaluronic acid filler intradermal injection with special injector is a safe and effective method for correction of nasojugal groove. Key Words: hyaluronic acid filler, injector, nasojugal groove

Introduction Nasojugal groove or infraorbital hollow is a 2 or 3 cm depression extending from the medial canthal region infrolaterally. It appears in the early stages of aging and is considered one of the landmarks of aging. It is characterized by a sunken appearance of the globe that results in the casting of a dark shadow over the nasal lower eyelid giving the patient a fatigued appearance (1,2). Recently hyaluronic acid (HA) dermal filler has become widely used for soft tissue augmentation and skin rejuvenation. The use of dermal fillers to correct infraorbital hollows has evolved as a rapid nonsurgical option to improve the appearance of this area. However, due to the delicate and vascular nature of this area, assessment of effectiveness and durability of the treatment has been limited (3). Several complications may occur with filler treatment in this area

such as edema, postinjection purpura, and arterial embolization of retinal artery (2). The specialized injector for HA contains 2 ml of HA. This unique injection device enables a controlled dose of 10 μl of HA gel per injection, so the clinician can focus entirely on placing the needle at the correct depth. This ensures that the HA filler is well suited to treat the thin and delicate skin areas. We performed a prospective randomized split face controlled study to evaluate the rejuvenation effects of HA injection on the nasojugal groove using specialized injector. Subjects and methods Patients and study design This was a single-center, prospective, randomized split face clinical study. All aspects of the protocol

Correspondence: Min Kyung Shin, MD, PhD, Department of Dermatology, College of Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Tel: ⫹ 82-2-958-8300. Fax: ⫹ 82-2-969-6538. E-mail: [email protected] (Received 16 January 2013 ; accepted 10 August 2013) ISSN 1476-4172 print/ISSN 1476-4180 online © 2014 Informa UK, Ltd. DOI: 10.3109/14764172.2013.854620

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Hyaluronic acid on nasojugal groove adhered to the Helsinki guidelines, and written informed consent was obtained from all subjects prior to any study-related procedure. Our study protocol was reviewed and approved by institutional review board of Kyung Hee medical center. It was planned that a total of ten patients would be enrolled into the study. Patients with prominent nasojugal groove or remarkable undereye dark shadow were treated with dermal filler. We injected stabilized hyaluronic acid-based gel of nonanimal origin (NASHA, Restylane Vital®, Q-Med, Uppsala, Sweden) using a specialized injector for this product (Restylane injector) (Figure 1). Patients were excluded if they had a known hypersensitivity to hyaluronic acid, if they were pregnant or breast feeding, and if they had an active skin disease. Patients who had been treated with other skin rejuvenation techniques in the previous 12 months were also excluded. Treatment was given in one session. Subjects were randomized and blinded to receive NASHA injection in treated side and saline injection in control side of infraorbital area. Filler was injected over the infraorbital hollow through three injection points using serial puncture injection technique. The level of injection for each patient was in the deep dermal plane. Treated areas were gently massaged immediately after the injection. The total injection volume of three injection points on treated side was 0.03 mL. The volume of saline was the visual endpoint which look like treated side (median volume: 0.15 mL). Follow-up visits were scheduled 4, 8, 12, and 24 weeks after the treatment. Assessment Assessments were performed before treatment, immediately after treatment, and at all follow-up visits. Patients were requested to self-assess treatment response of volume and skin tone correction using a 3 point scale (1: improved, 0: no change, ⫺ 1: worsen). For objective evaluation, photographs were taken at every visit. To standardize photographs,


patients were positioned at the same distance and angle from the camera; identical lighting conditions were used for each patient. Images were taken, stored, retrieved, and browsed through VISIA® Complexion Analysis System (Canfield Scientific Inc., Fairfield, NJ, USA). The effect of volume correction was analyzed by three blinded clinicians with the clinical photos using the same 3 point scale (1: improved, 0: no change, ⫺ 1: worsen). The effect of skin tone correction was assessed by spectrophotometer and mexameter at every visit. The measurement was also performed by a blinded clinician. Possible adverse events following filler injection were recorded at every visit. Statistical analysis All data were analyzed using SPSS version 12.0 (SPSS V12.0K, SPSS Inc., Chicago, IL, USA). Paired Student’s t-tests were used to compare all preand post-therapy values. In all cases, p values less than 0.05 were defined as statistically significant. Results Patients All aspects of this study were performed at the Kyung Arumdaun Nara Dermatologic Clinic located in Seoul, Korea. In total, ten Korean female patients with prominent nasojugal groove or dark undereye circle were subjected to filler treatment. Patients ranged in age from 27 to 59 years, with an average age of 31.2 years. Fitzpatrick skin types 4 through 5 were represented in our cohort. Subjective satisfaction score All patients reported satisfaction with their treatment. The mean score at the 4-week follow-up visit was 0.8. Two patients noticed not only volumetric correction but also improvement of their dark

Figure 1. Specialized filler injector.

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H.-K. Lim et al.

Figure 2. Mean subject satisfaction scores at follow-up visits.

circle on the treated side. The score of treated side gradually decreased over time, but still maintained higher score at last follow-up visit compared with that of control side. The results of mean scores of each follow-up visits are summarized in Figure 2. Objective improvement score Three blinded clinicians analyzed clinical photographs of patients and scored overall improved state. The mean score on the treated side was statistically higher than control side at 4-week and 8-week follow-up visits. The relatively short duration of effectiveness can be explained by the character of Restylane Vital® which can be easily integrated into the skin than conventional fillers. This character helps to correct more naturally even though the patient may be required repetitive treatment in some cases. And using relatively small amount of filler is also one of the causes for short duration. The objective improvement of treated side was maintained at the last follow-up, although the difference with the untreated side was not statistically significant (Figure 3). To assess and

quantify skin tone correction of the dark circle, spectrophotometer and mexameter were used. Erythema index by spectrophotometer was lower on treated side when checked immediately after treatment and did not show significant change thereafter (Table I). Melanin index by mexameter showed a significant difference at the 4-week follow-up visit which implies the skin tone correction by dermal filler is most effective after 1 month of treatment (Figures 3 and 4). Improvement of skin tone was correlated to volumatic correction. As decrement of volumatic effect, melanin index of treated area slowly return close to its original value. Adverse events There were no serious adverse events reported. No patients in this study required reduction of volume by means of hyaluronidase injection. Mild treatment-associated adverse events, such as redness, swelling, and ecchymosis, were commonly reported yet transient in nature, typically lasting less than 1 week. No patient exhibited the Tyndall effect.

Figure 3. Objective improvement score of treated side.

Hyaluronic acid on nasojugal groove


Table I. Data of erythema index and melanin index. Erythema index (mean ⫾ S.D.)

Melanin index (mean ⫾ S.D.)

Measured time

Treated side

Control side

Treated side

Control side

Baseline Immediately after treatment 4 weeks 8 weeks 12 weeks 24 weeks

59.67 ⫾ 0.08 57.67 ⫾ 0.08

59.82 ⫾ 0.11 59.68 ⫾ 0.08

154.03 ⫾ 1.47 146.56 ⫾ 0.73

153.36 ⫾ 0.52 143.56 ⫾ 0.58

60.61 ⫾ 0.12 60.11 ⫾ 0.13 60.20 ⫾ 0.12 60.86 ⫾ 0.05

59.98 ⫾ 0.11 60.11 ⫾ 0.08 60.29 ⫾ 0.15 60.84 ⫾ 0.07

142.59 ⫾ 0.22 145.03 ⫾ 0.33 148.36 ⫾ 0.41 146.75 ⫾ 0.34

154.36 ⫾ 0.33 150.74 ⫾ 0.52 152.00 ⫾ 0.46 151.20 ⫾ 0.51

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S.D.: standard deviation

Discussion Subtle changes in skin color and consistency, subcutaneous fat atrophy, and changes in the underlying bony substructures are responsible for the appearance of the aged individual. The development of dark circles under the eyes due to nasojugal groove is one of the early signs of periorbital aging, lending a fatigued and aged appearance to the face. Loeb, in 1961, used the term “nasojugal groove” to describe the concavity at the border of the eyelid and the cheek medially. Flowers, in 1969, first named this groove the ‘tear trough’. Volume loss of orbital rim seems to predominate in development of nasojugal groove. However, orbital fat herniation, skin laxity, and possible ptosis of tissues below secondary to volumetric changes or other reasons could also play a role (1,4). Nonsurgical correction in this area includes autologous fat graft and filler injection. Although injection of HA products is generally well tolerated, some serious complications are of particular concern when utilized in the periorbital region. Arterial occlusion of the retinal artery either by direct injection or by compression is a rare but serious risk seen with filler injection in this anatomic area. Many superficial arteries of the periorbital area are distal

branches of the ophthalmic artery. Retinal artery is the proximal branch of ophthalmic artery. Therefore, even if a tiny amount of the filler enters into the arteries, it can cause blockage of retinal artery which can lead to blindness (1,5,6). Although cutaneous necrosis due to filler has been usually reported on glabellar area (7), it is a theoretical yet significant complication that can be happened on periorbital area. Injections that are too superficial can yield the appearance of a bluish tint secondary to the Tyndall effect (8). Postinjection purpura and swelling are possible events after injection at periorbital area. Correction of the tear trough requires precise volume augmentation, as even slight overcorrection will result in an unacceptable appearance. Most previous studies injected filler on the periosteal plane using a plain syringe. One study measured the volume of tear trough for quantitative analysis of periorbital aging with a threedimensional surface imaging tool. A consistent pattern of volume difference and regression of soft tissues associated with the medial canthus nasojugal groove was seen in the aged individuals. The volume difference associated with the tear trough ranged from 0.02 cc to 1.27 cc with median values of 0.38 cc and 0.42 cc (9). Rough average

Figure 4. Melanin index of treated side.

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H.-K. Lim et al. safely. We used a much smaller amount of filler for correction compared with other conventional studies. This may effect the relative decrement of some patients’ satisfaction score. When filler is injected on the periosteal plane, visual volume expansion effect can be attenuated more than actually used amount of filler because of surrounding tissue. However, we injected filler with intradermal method and the volumatic effect was directly shown without loss. Therefore, despite the relatively small amount of filler, it was possible to quickly see results. Further large-scale and long-term follow-up studies will be necessary to demonstrate adequate filler materials and injection skills for a prolonged effect of nasojugal groove correction.

Figure 5. Photographs of representative case taken (A) before treatment and (B) 24 weeks after treatment (right side: normal saline, left side: HA filler).

volume of filler injected for correction of nasojugal groove was 0.2–0.5 cc on each side (2,10). Most adverse events can happen when the clinician tries to place filler into a deep layer as a conventional method. We used a modified method of intradermal injection of filler. Compared with conventional periosteal plane injection, intradermal injection requires more delicate superficial injection skill and smaller amount of filler. Therefore, Restylane Vital® injector specialized for injection of certain volume of filler (10 μl per shot) with great convenience could aid more precise procedure in our study. At last follow-up in 6 months, 50% of patients reported satisfaction compared with their status before treatment (Figure 5). Objective assessment by blinded clinicians revealed less effect than patients’ assessment. The statistically significant effect was maintained until 8 week follow-up. Skin tone of dark circle was measured objectively by mexameter. The effect of correction of dark circle showed peak at 4-week follow-up. This study is a controlled split face study. Due to the simple study design, it is reasonable to interpret the results with confidence. To inject accurate volume of filler, we used specialized filler injector. Injectors have been seldom used in correction of nasojugal groove and we found that the injector can help when performing delicate procedure in this area

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

References 1. Hirmand H. Anatomy and nonsurgical correction of the tear trough deformity. Plast Reconstr Surg. 2010;125:699–708. 2. Hirsch RJ, Carruthers JD, Carruthers A. Infraorbital hollow treatment by dermal fillers. Dermatol Surg. 2007;33: 1116–1119. 3. Bosniak S, Sadick NS, Cantisano-Zilkha M, Glavas IP, Roy D. The hyaluronic acid push technique for the nasojugal groove. Dermatol Surg. 2008;34:127–131. 4. Pessa JE, Desvigne LD, Lambros VS, Nimerick J, Sugunan B, Zadoo VP. Changes in ocular globe-to-orbital rim position with age: implications for aesthetic blepharoplasty of the lower eyelids. Aesthetic Plast Surg. 1999;23:337 5. Saylan Z. Facial fillers and their complications. Asthetic Surg J. 2003;23:221–224. 6. Schanz S, Schippert W, Ulmer A, Rassner G, Fierlbeck G. Arterial embolization caused by injection of hyaluronic acid (Restylane). Br J Dermatol. 2002;146:928–929. 7. Glaich AS, Cohen JL, Goldberg LH. Injection necrosis of the glabella: protocol for prevention and treatment after use of dermal fillers. Dermatol Surg. 2006;32:276–281. 8. Hirsch RJ, Narurkar V, Carruthers J. Management of injected hyaluronic acid induced Tyndall effects. Lasers Surg Med. 2006;38:202–204. 9. Camp MC, Wong WW, Filip Z, Carter CS, Gupta SC. A quantitative analysis of periorbital aging with threedimensional surface imaging. Plast Reconstr Aesthet Surg. 2011;64:148–154. 10. Donath AS, Glasgold RA, Meier J, Glasgold MJ. Quantitative evaluation of volume augmentation in the tear trough with a hyaluronic Acid-based filler: a three-dimensional analysis. Plast Reconstr Surg. 2010;125:1515–1522.

Rejuvenation effects of hyaluronic acid injection on nasojugal groove: prospective randomized split face clinical controlled study.

Pronounced nasojugal groove (tear trough deformity) is one of the landmarks of aging. Hyaluronic acid filler can be used for attenuating the nasojugal...
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