Introduction

The importance of volume changes in an aging face is well recognized, and autologous facial fat grafting is being used with increasing popularity. While facial rhytidectomy techniques may improve soft tissue descent and deep creases on the face, these procedures do not address the underlying volume loss that occurs due to senile fat atrophy thoroughly. Since the introduction of Coleman’s fat grafting technique [1], volumetric restoration using autologous fat has become an integral part of rejuvenation. The technique is simple and largely safe.

However, autologous fat grafting can produce variable results, and objective, credible evaluation of volume replacement therapy is still lacking. The amount of fat to be injected to each facial compartment is typically based on surgeon’s experience rather than based on scientific data. Success of intervention has traditionally relied on patient satisfaction rather than quantitative analysis of volume change. Scant data exist on the retention of fat volume in a clinical setting [2].

The volume of fat to inject in each facial compartment during autologous fat grafting remains poorly standardized, leading to unsatisfactory results in some patients and a slow learning course. Here we systematically review the literature to elucidate volumes of fat injected in each facial subunit.

Materials and Methods

Study Design

We conducted a systematic literature review to assess the volume injected to each area of the face for volumetric rejuvenation. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol and performed a MEDLINE database search via PubMed in November–December 2016 using the keywords “facial,” “fat grafting,” “lipofilling,” “Coleman technique,” “autologous fat transfer,” and “structural fat grafting.” We also reviewed the references of retrieved articles to search for other potentially relevant research articles.

Inclusion Criteria

All relevant articles in which study participants received facial fat grafting for aging were reviewed. We included prospective and retrospective observational studies, case series, and case reports. We excluded review articles, animal studies, articles written in languages other than English, and articles that studied fat grafting for purposes other than aging (e.g., trauma, scars, congenital disorders). We also excluded articles not reporting volumes of fat injected (in mL) and not reporting the facial subunits injected.

Data Collection

Two independent reviewers read the titles and abstracts of retrieved articles. The full text was retrieved. The following data points were recorded: author(s), year of publication, study design, sample size, donor site, fat injection technique, average and range of volume injected, duration of follow-up, percentage of volume retention, and complications.

Results

A total of 2145 articles were initially identified by our MEDLINE search, and 19 articles with 510 patients were included in this systematic review (Fig. 1). The types of articles included case reports [3], case series [1, 4, 5], prospective studies [2, 6,7,8,9,10,11,12,13], retrospective studies [14,15,16,17,18], and observational studies [19]. The sample size ranged from 1 to 83 patients per article (Table 1). The range and average amount of fat injected to each area of the face is depicted in Fig. 2. Rhytidectomy was the most common concurrent procedure performed along with facial fat grafting (7 articles). Fat was harvested from the abdomen, hips, thighs, buttocks, flank, lower abdomen, periumbilical area, trochanteric area, knee, submental area, and neck. Percent of fat retention at follow-up was objectively measured using 3D photography or 2D photography in three articles [2, 7, 12] and subjectively measured by the surgeon in two articles [11, 16].

Fig. 1
figure 1

Flowchart of article research

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Table 1 All articles included in systematic review
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Fig. 2
figure 2

Average and range of fat injected to each area of the face. asterisk amount injected per side

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Forehead and Glabella (Table 2)

Three studies with 11 subjects measured fat injection to the forehead [4, 5, 9]. The average volume injected was 6.5 mL with range of 4.0–10.0 mL. Four studies with 30 subjects measured fat injection to the glabellar region [5, 6, 14, 16]. The average volume injected was 1.4 mL with range of 1.0–4.0 mL. No objective information on retention rate was given.

Table 2 Volume injected to forehead and glabellar region
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Temple (Table 3)

Five studies with 47 subjects measured fat injection to the temple [4, 5, 13, 16, 19]. The average volume injected was 5.9 mL with range of 2.0–10.0 mL per side. No objective information on retention rate was given.

Table 3 Volume injected to temple
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Periorbital (Table 4)

One study with seven subjects measured fat injection to the eyebrow [6]. The average volume injected was 5.5 mL per side. Two studies with three subjects reported fat injection to the upper eyelid [4, 5]. The average volume injected was 1.7 mL with range of 1.5–2.5 mL per side. One study with eight subjects included fat injection to the tear trough [14]. The average volume injected was 0.65 mL with range of 0.3–1.0 mL per side. Four studies with 19 subjects measured fat injection to the infraorbital area (infraorbital rim to lower lid/cheek junction) [4,5,6, 18]. The average volume injected was 1.4 mL with range of 0.9–3.0 mL per side. No objective information on retention rate was given.

Table 4 Volume injected to periorbital area
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Cheek and Midface (Table 5)

Four studies with 91 subjects measured fat injection to the midface [2, 7, 8, 19]. The average volume injected was 8.7 mL with range of 1.0–22.5 mL per side. The midface was further subdivided into cheek, buccal region, posterior buccal cheek, lateral malar, anterior malar fold, anterior malar region, zygomatic area, or “cheeks, lower eyelids, zygomatic region.” Four studies with 118 subjects measured fat injection to the cheek [5, 11,12,13]. The average volume injected was 25.7 mL with range of 4.0–47.0 mL per side. Two studies with 24 subjects measured fat injection to the zygomatic area [6, 13]. The average volume injected was 4.7 mL with range of 3.0–10.0 mL per side. Gerth et al. noted 41.2% volume retention in the midface after 17 months [7]. Meier et al. noted 31.8% volume retention in the midface after 16 months [2]. Wang et al. noted 27.1% volume retention in the cheek after 12 months [12]. Gerth et al. and Meier et al. used 3D photography to measure volume retention, while Wang et al. used 2D photography to measure volume retention.

Table 5 Volume injected to cheek and midface
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Nasolabial Fold (Table 6)

Seven studies with 38 subjects measured fat injection to the nasolabial folds [1, 3,4,5,6, 16, 19]. The average volume injected was 2.8 mL with range of 1.0–7.5 mL per side. No objective information on retention rate was given.

Table 6 Volume injected to nasolabial fold
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Perioral (Table 7)

Six studies with 25 subjects measured fat injection to the upper lip [1, 3,4,5, 14, 19]. The average volume injected was 3.0 mL with range of 1.0–5.0 mL. Five articles with 24 subjects measured fat injection to the lower lip [3,4,5, 14, 19]. The average volume injected was 3.7 mL with range of 2.5–6.0 mL. Four studies with 33 subjects measured fat injection to the marionette lines [4,5,6, 19]. The average and range of fat injected was 1.3 mL with range of 1.0–3.5 mL per side. No objective information on retention rate was given.

Table 7 Volume injected to perioral region
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Mandibular Area (Table 8)

Three studies with 18 subjects measured fat injection to the mandibular area [3, 5, 13]. The average volume injected was 11.5 mL with range of 4.0–27.0 mL per side. No objective information on retention rate was given.

Table 8 Volume injected to mandibular area
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Chin (Table 9 )

Three studies with six subjects measured fat injection to the chin [3, 5, 13]. The average volume injected was 6.7 mL with range of 1.0–20.0 mL. No objective information on retention rate was given.

Table 9 Volume injected to chin
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Discussion

Fat grafting has evolved and improved since Neuber first introduced the idea in 1893 [20]. Coleman popularized this technique that has become an essential part of facial rejuvenation and harmonization [1]. The goal of autologous fat grafting for an aging face is to create a natural, rejuvenated appearance. This requires knowledge of the aging process and an understanding that facial subcutaneous fat is not a “confluent mass” but rather a highly compartmentalized arrangement [21]. The changes that occur as the face ages are well described [21,22,23,24,25]. Briefly, volume loss in soft tissue and bony structures is an inherent part of the aging process. In a young face, fat is homogeneously distributed, creating a full face without demarcation of subcutaneous regions. The young face is made up of a prominent jawline, convex temples, lateral projection of cheeks, and multiple smaller arcs of the lips [24]. As the face ages, the anatomical compartments become more well defined, leading to abrupt contour changes and disharmony. Unlike the young face, which stores fat evenly, the subcutaneous fat in an older person gets redistributed, leading to atrophy in some areas and hypertrophy in others [24]. Atrophy typically occurs in the forehead, temporal, periorbital, buccal, and perioral areas. Hypertrophy typically occurs submentally, in the jowl, lateral nasolabial fold, lateral labiomental crease, and lateral malar areas [24]. Additionally, the maxilla and mandible become thinner, lips become straight or angular, and the forehead loses its anterior projection [24]. However, fat injection’s unpredictable resorption is still a major limitation.

Multiple interventions are currently available to achieve volumetric rejuvenation. Lifting procedures, though commonly performed to achieve a more youthful appearance, do not address the issue of volume loss that occurs due to craniofacial remodeling and fat atrophy. Bone-mobilization techniques are invasive and are associated with higher morbidity [26]. Injectable fillers, such as hyaluronic acid, collagen, and poly-L-lactic acid, have been used to restore facial volume. Their shortfalls include the results being temporary, cost, and potential adverse allergenic reactions [27]. Autologous fat transfer, on the other hand, is cost efficient, biocompatible, and abundant for most patients.

We, like others, have anecdotally found fat injection safe with long-lasting results. There is growing consensus among surgeons to use fat injection to further augment facelift results [28]. There is no scientific evidence suggesting that a specific site demonstrates increased viability of injected fat. However, it is uniformly believed that fat injection is more successful in more static anatomic areas. Best results are usually obtained when less than 0.1 mL aliquots are injected to promote revascularization of the grafts.

Volume retention is multifactorial and depends on how the fat is harvested, processed, transplanted, and managed [29]. These factors have been studied in various laboratories, but no consensus exists in the literature thus far [30]. Using a larger bore cannula to harvest the fat generally helps maintain the cellular architecture and maximize the number of cells within fat particles [30]. The grafted fat should be placed within 0.2 cm from arterial blood supply to avoid central necrosis [31] and prevent complications such as hematoma, oil cysts, and calcifications [30]. As the total volume of transplanted fat increases, there is increased likelihood of central necrosis and lower volume retention [32]. Recent advances to improve graft retention have introduced the use of adipose-derived stem cells (ASCs) and platelet-rich plasma (PRP) [33]. A randomized clinical trial in 2015 found that adding plasma rich in growth factors to the grafted fat did not make a significant difference in volume retention [34]. Further research will be required to elucidate clinical efficacy.

Clinical data on volume retention overtime are limited. In our systematic review, only three articles included objective assessment of volume retention during follow-up, and two of the studies provided a subjective estimate when documenting this value. Instead, most articles in our study measure fat grafting success using surgeon and patient’s satisfaction. This lack of objective data has led many patients to receive multiple touch-up surgeries before they are satisfied with their results.

To our knowledge, this is the first review that specifically tries to quantify the volume of fat typically injected during fat grafting for facial aging. Many limitations exist in this systematic review. Few studies assessed volume retention at long-term follow-up. More recent development of 3D imaging may be utilized to provide an objective assessment of volume retention, though to date 3D photography has only been studied in the midface [2, 7]. Comparing before-and-after photographs can be misleading due to variability in film color, position, flash intensity, and facial expression [1]. Radiographic imaging may also be utilized to objectively evaluate volume loss. Fontdevila et al. have utilized computed tomography to quantify volume retention after facial fat grafting in HIV patients with facial lipoatrophy in two studies [34, 35]. Magnetic resonance imaging has also been used in studies to measure facial fat atrophy overtime [36,37,38,39]. Use of magnetic resonance imaging to measure volume retention after fat grafting to the breast has helped to standardize injection techniques [40].

The anatomic specificity reported by each author varies greatly and limits comparison between studies. For example, when describing the midface, studies we incorporated into our review use “midface,” “cheek area,” “buccal region,” “posterior buccal cheek,” “lateral malar,” “anterior malar fold,” “anterior malar region,” “zygomatic area,” and “cheeks, lower eyelids, zygomatic region.”

The biggest limitation to this study is the lack of reporting in the literature to draw from. Despite the ubiquity of fat grafting [35] and extensive laboratory research, little has been done to define its efficacy in patients. We included all relevant studies in our systematic review, including case reports and case series. Surgeons must rely on understanding of anatomy and individualized patient need based on bony and soft tissue changes to determine injection volume. Additionally, it is critical to understand each patient’s goals, as some patients wish to address facial aging and others to enhance a certain feature. Therefore, the findings in this systematic review are not intended to be general guidelines. Nonetheless, this paper can serve as a starting point for the less experienced surgeon, a base for research, and a clinical estimate that must be adjusted based on each patient’s unique needs.

Conclusion

Here we undertake a systematic review of the literature to better understand volumes of fat injected to different facial subunits. To determine volumetric needs and retention rates, we encourage standardization of terminology and further reporting of injection volumes and outcomes.