Introduction

Physicians and patients continue to strive for the ‘ideal filler’, which would offer consistent, sustained results that remain natural and free of complications over time and that would be biocompatible, safe, cost-effective, and versatile. Injected properly, highly purified liquid injectable silicone (HPLIS) meets the majority of these criteria. Although use of injectable silicone has historically been met with controversy, when more modern HPLIS is properly injected in small amounts with the microdroplet technique with repeat treatments spaced weeks apart, the physician may routinely achieve optimal and enduring correction of scars, rhytides, and facial atrophy.

HPLIS may be much less forgiving than temporary fillers and is a potential liability when it is injected incorrectly, results in undesired augmentation, or serves as a nidus for inflammation and infection. Therefore, experience and precise technique are important to achieve good outcomes. Physicians should use HPLIS only after extensive training in proper technique and patient selection. Candidates for treatment should have clear treatment objectives and understand that multiple treatment sessions may be required to achieve optimal correction. Patients who desire immediate correction or are uncertain of their treatment goals are better treated with shorter duration, temporary fillers rather than HPLIS.

Basic science

Silicon (Si) is a relatively inert element that is essential to humans in small amounts, and is second only to oxygen as the most abundant element of the Earth’s crust. ‘Silicone’ describes a group of synthetic polymers containing elemental silicon. Polymers in the silicone family may exist in solid, liquid, and gel states, with various chemical, physical, and thermal properties. Silicone polymers also vary with regard to purity, sterility, and biocompatibility. Although various silicone polymers are employed for medical use, polydimethylsiloxane is the liquid injectable silicone used for soft tissue augmentation. The molecular structure of this colorless, odorless, non-volatile oil consists of repeating dimethylsiloxane units with terminal trimethylsiloxane ends.

The viscosity of a given liquid silicone product is dependent upon the mean number and chain length of the dimethylsiloxane subunits within the polymer, with longer chain molecules conferring a higher viscosity. Viscosity is measured in centistokes (cs), where 1 cs equals the viscosity of water. Current HPLIS is either 1000 cs (similar to the viscosity of honey) or 5000 cs.

Silicones have not been found to be carcinogenic, and have demonstrated ‘an enviable record of safety’ according to a 1998 National Science Panel investigating silicone implants reported by Diamond and colleagues. HPLIS is not altered in vivo, although small amounts may be phagocytized and enter the reticuloendothelial system.

Mechanism of action

HPLIS first creates immediate volume enhancement by a direct space-filling effect. Additional filling occurs by the deposition of new collagen via fibroplasia. After injection, a localized inflammatory reaction ensues consisting of neutrophil migration and some degree of macrophage phagocytic activity, with fibroblasts depositing a thin-walled collagen capsule around the silicone microdroplet. This capsule effectively anchors the microdroplet in place and prevents migration. Several filler products, both temporary and permanent, were reported by (DHJ) in 2009 to induce collagen fibroplasia as a partial mechanism of action for aesthetic improvement.

Rather than attempting to reach optimal correction in one session, fibroplastic fillers require that smaller amounts of product be injected over several sessions spaced 1–2 months apart or longer. This avoids overcorrection by allowing the fibroplastic process adequate time to occur prior to subsequent treatment sessions.

Controversy

The past several decades have witnessed notable debate regarding the safety of liquid injectable silicone, with both critics and advocates arguing their positions based largely on anecdotal data rather than rigorous trials. The true number of patients treated with liquid silicone available prior to 1990 who have historically experienced treatment success versus significant complications is simply unknown.

A further difficulty in historically analyzing the safety of ‘silicone’ as an augmenting agent is that, apart from the modern, US Food and Drug Administration (FDA)-approved products available since the 1990s, an unknown number of products claiming to be silicone have likely been adulterated, impure, or non-silicone substances altogether. Although highly purified 1000 and 5000 cs products intended for injection into the human body were FDA approved for human use in the 1990s, various substances masquerading as ‘silicone’ have been injected for the past 60 years, at times with significant complications, as reported by Delage et al, Baselga & Pujol and Rapaport et al. Even products labeled as ‘medical-grade’ silicone have not historically been regulated or authenticated. A 1989 analysis by Parel of six ‘medical-grade’ silicone oils commonly used for injection revealed six different products of variable viscosity, each with significant amounts of elemental impurities and low-molecular-weight adulterants that can produce inflammatory and granulomatous reactions.

Critics argue that liquid silicone is an inherently unpredictable implant, fraught with potential complications. Several anecdotal reports of complications such as cellulitis, nodules, granulomatous reactions, and migration have been described by the groups above, although variables such as product purity, volume, and injection technique could not be established with certainty. Furthermore, complications were reported by Rapaport et al to occur as long as 36 years after treatment. Migration of product to other areas of the body may occur when large boluses of liquid silicone are injected, but this has never been reported when using the microdroplet technique, as in the studies by Duffy in 2005 and Price and colleagues in 2006.

Advocates posit that HPLIS is extremely safe and beneficial when three rules of injection are strictly followed: (1) use only FDA-approved products intended for injection into the human body, (2) exclusively employ the microdroplet technique, and (3) strictly follow a protocol utilizing limited volumes injected over multiple sessions spaced monthly or longer.

Several authors have published excellent safety records of longer term follow-up on patients treated with liquid silicone. Wallace and colleagues reported long-term follow-up over 41 years using liquid silicone as a soft tissue substitute for plantar fat loss in over 1500 patients, with 25 000 recorded silicone injections; they found that the host response to injections consisted of a ‘banal and stable fibrous tissue formation’. Other authors including Jones et al, Orentreich & Leone, and Hevia have published multiple reports of their extensive and successful experience with liquid silicone, and reiterate that the three principles of product purity, appropriate technique, and proper protocol are imperative for success. Duffy, who has written extensively on the subject, gathers that liquid injectable silicone (LIS) has been used for soft tissue augmentation worldwide for at least 40 years, and hypothetically in at least 200 000 patients in the USA. He cautions that, although pure liquid silicone may be a superior filler for the permanent correction of certain defects, physicians who use it must realize that its misuse, or the use of other materials masquerading as pure silicone, have created ‘a pervasive climate of distrust and a veritable minefield of extraordinarily unpleasant medico-legal possibilities’. Such perceptions reiterate the importance of ongoing trials as they replace anecdotal reports with more rigorously obtained data. Despite 60 years of use, only within the past decade have well-designed trials begun with the newer generation of standardized, highly purified products injected according to strict protocol. These studies have so far demonstrated an excellent profile of safety and efficacy. Collection of ongoing objective data and longer term follow-up are necessary to provide clarity into the true risks and benefits of soft tissue augmentation with modern HPLIS.

Indications and patient selection

Although there are currently no FDA-approved cosmetic indications for HPLIS, it may be legally injected off-label for the augmentation of HIV-associated facial lipoatrophy, nasolabial folds, labiomental folds, mid-malar depressions, lip atrophy, hemifacial atrophy, acne scarring, other atrophic scarring, age-related atrophy of the hands, corns and calluses of the feet, and healed diabetic neuropathic foot ulcers (see the studies by Orentreich, Balkin, and Fulton et al) (Figs 10.1–10.4). HPLIS is specifically contraindicated for injection into the breast, eyelids, or bound-down scars or injection into an actively inflamed site. Its safety has not been studied in pregnant women. It should not be injected into patients with chronic bacterial sinusitis, dental caries, other active bacterial infection, or in those who may be predisposed to trauma in the treated area. Additionally, HPLIS is not a substitute for surgical lifting, chemical or laser resurfacing, dermabrasion, or treatment of dynamic rhytides with botulinum toxin. The ideal patient is one with appropriate insight into the permanent and off-label nature of LIS, a realistic attitude regarding achievable results, in good physical health, and compliant with recommendations. Patients seeking immediate correction or temporary augmentation should be treated with temporary fillers. Serious consideration by both the patient and physician must be given to the longevity of results obtained with HPLIS. Although permanent fillers may be preferred to temporary fillers owing to their longevity, one must consider the possibility that personal and societal aesthetic goals may change over time. Furthermore, an undesirable result will be unlikely to diminish with time and may be difficult to correct.

Figure 10.1 A: HIV facial lipoatrophy. B: After correction with a series of monthly injections with Silikon-1000. C: 10 year follow up.

Figure 10.2 A: HIV facial lipoatrophy after Goretex thread implants. Note the uneven facial contour. B: After a series of monthly injections with Silikon-1000 to restore volume and even countour. C: 10 year follow-up.

Figure 10.3 A: Acne scarring. B: After a series of injections with Silikon-1000.

Figure 10.4 A: Acne scarring. B: After a series of injections with Silikon-1000.

The above indications for HPLIS are also well served by modern, temporary fillers such as hyaluronic acid, calcium hydroxylapatite, and poly-l-lactic acid. However, in the authors’ opinion, HPLIS is the most practical, and has been demonstrated as an excellent choice, for the correction of more severe HIV-related facial lipoatrophy where large volumes and a durable correction are required. Those affected may be stigmatized, leading to psychological distress, social and career impediments, and impaired compliance with HIV medications. Temporary treatment options are limited by excessive cost and necessity of frequent treatments. An open-label pilot trial by Jones and colleagues published in 2004 evaluated the safety and efficacy of highly purified 1000 cs silicone oil injected by microdroplet technique for the treatment of HIV-associated lipoatrophy. Data on 77 patients with a complete correction were analyzed and it was determined that the volume of silicone, number of treatments, and time required to reach optimal correction were directly related to initial severity of lipoatrophy (P < 0.0001). Supple, even facial contours were routinely restored, with all patients tolerating treatments well. About 3-monthly treatments using 2 mL of HPLIS were required for each stage of severity on the James / Carruthers lipoatrophy severity rating scale. No initial adverse events were noted. In this pilot trial, it was demonstrated that highly purified 1000 cs silicone oil is a safe and effective treatment option for HIV facial lipoatrophy.

More recently the author (DHJ), reported in 2010 on safety outcomes in 135 patients with 5-year and beyond follow-up after treatment with HPLIS for HIV-associated facial lipoatrophy (HIV FLA). Four of the 135 patients experienced granulomatous-type reactions (firm induration) over 5 or more years. All events responded completely to IL triamcinolone and minocycline, and none were considered serious. The specific histories of each patient support a bacterial and / or and immunological basis for such reactions.

Using the microdroplet, multiple-injection technique, Barnett & Barnett have had success with injections of LIS for acne scars lasting over a 10-, 15-, and 30-year follow-up period (as reported by the author (DHJ) in 2010).

Materials

The most appropriate HPLIS for off-label soft tissue augmentation is Silikon-1000 (Alcon, Fort Worth, TX) (Fig. 10.5); 5000 cs Adatosil (Bausch & Lomb, Rochester, NY) may also be used off-label, but is too viscous to inject through small-gauge needles. A 0.5 mL of LIS is drawn through a 16-gauge Nokor needle into a 1 mL Becton Dickinson (BD) Luer-Lok® syringe (Fig. 10.6) using sterile technique. As molecules from the rubber stopper of the syringe could theoretically contaminate the HPLIS after a long exposure period, it should be drawn into the injecting syringe immediately prior to treatment, and should never be stored in the syringe. HPLIS is most easily injected through a 27-gauge 0.5-inch (6 mm) Kendall Monoject aluminum-hubbed needle. Plastic-hubbed needles tend to pop off with the higher injection pressures needed for injection through smaller gauge needles. To increase injector comfort, 0.5-inch inner diameter rubber electrical bushings purchased from a hardware store may be autoclaved and placed over the barrel of the syringe to cushion the physician’s second and third fingers during injection.

Figure 10.5 Silikon-1000, which is specifically FDA-approved for ophthalmic use, but may be legaly used off-label for skin augmentation.

Figure 10.6 Instrumentation; from top to bottom, 1 cc BD syringe, 27-gauge \xC21/2 inch needle, autoclaved electrical bushing, 16-gauge needle.

Patient preparation

As with all fillers, patients should avoid aspirin, non-steroidal anti-inflammatory preparations, and anticoagulants for 7–10 days prior to injection. It is mandatory to discuss with the patient the risks, benefits, and alternative treatments to HPLIS and document this prior to injection. Patients must understand that HPLIS is a permanent filler, and must understand that it is being used off-label. Written informed consent must be obtained.

Furthermore, high-quality pre-treatment photographs should be taken. Makeup is removed, and the skin is washed with an antibacterial cleanser and prepared with a povidone–iodine antiseptic or other surgical preparatory solution. Areas to be injected are outlined under good lighting with the patient in a sitting position, using a fine-tip marking pen. Target areas for volume restoration should be marked in both the smiling and resting position, as these often change remarkably with facial activity. When treating HIV facial lipoatrophy, mid-malar depressions often become slightly elevated on smiling, and overcorrection of this area may result in a ‘chipmunk’

appearance when the patient smiles. A topical anesthetic such as lidocaine or other topical amide mixture is then placed on the treatment area and wiped off after 30 minutes with clean gauze.

Injection technique

Although temporary fillers may be injected with varied techniques, HPLIS should be injected only by the microdroplet technique originally described in 2006 by Orentreich. Other injection techniques risk undesirable consequences, including pooling or beading of silicone macrodroplets in the injection tract and possible migration via escape from the anchoring fibroplastic capsules. A microdroplet is defined as 0.005–0.01 mL of product, an amount that possesses a very large surface area to volume ratio. A larger surface area to volume ratio effectively allows the microdroplet to be anchored into place by the ensuing fibroplasia around the periphery. With larger macrodroplets, defined as >0.01 mL, encapsulation may not be sufficient to prevent product migration. A given volume of HPLIS dispersed into many microdroplets provides for a greater total surface area than would be provided by fewer, larger droplets. Maximizing the total surface area of injected product effectively maximizes the degree of augmentation.

Injections are made into the immediate subdermal plane or deeper. Often, as the needle enters the subdermal plane, there is a slight give in the tissue resistance to the needle. Intradermal injection should be diligently avoided, as it may result in dermal erythema and ridging. Attention should be given to make sure that the needle is in the subdermal plane prior to depressing the plunger. Furthermore, the injector’s thumb should be removed from the plunger prior to removing the needle. Injections should be placed at 2–5 mm intervals along the skin surface at the optimal angle for penetration and deposition into the subdermal plane. The optimal angle varies with the intended depth of LIS placement. For areas where deeper placement is desired, a more oblique (approaching perpendicular to the skin surface) angle of insertion is best, whereas a more acute (approaching parallel to the skin surface) angle of insertion works best for more superficial deposition.

As a rule, multiple passes over the same treatment area in a single session should be avoided, although experienced injectors may sometimes make a second pass at a different subcutaneous level and use a tunneling technique to inject microdroplets in different subdermal areas. Importantly, greater correction should be accomplished over a longer period of time rather than with a larger per-session volume. Per-session treatment volumes should be limited to 0.5 mL for smaller surface areas such as the nasolabial fold, and no more than 2.0 mL for larger surface areas such as facial lipoatrophy. Such per-session volumes allow around 100–200 individual microdroplet deposits at 2–5 mm intervals, allowing a large treatment area to be covered in a single session if necessary.

Injection sessions should be spaced at least 1 month apart, or more, to allow for a limited fibrous tissue reaction to occur around each silicone microdroplet. Overcorrection should be avoided. As optimal correction approaches, treatment intervals should be extended to allow complete deposition of fibrous tissue prior to the next injection.

Side effects and managing complications

The immediate injection-related side effects commonly seen with all fillers occur with HPLIS as well. Needle-associated pain is usually well controlled with pre-treatment topical lidocaine anesthetics. Occasionally, pre-treatment with oral analgesics (e.g. 0.5 mg alprazolam and two tablets of acetaminophen / hydrocodone 5/500 mg) 1 hour prior to treatment may be necessary in the pain-intolerant patient. Mild post-injection edema and erythema are common, and resolve within a few days. The transient edema may even be representative of what optimal correction may look like after several treatments. Purpura, when it rarely occurs, usually resolves within a few days and may be treated with a pulsed dye laser to hasten resolution.

When injected with the appropriate technique, LIS is remarkably similar in texture and sensation to natural soft tissue. However, when larger cumulative volumes are injected, as in HIV facial lipoatrophy, the treated area may occasionally feel slightly rubbery and firmer than natural soft tissue. Migration of injected liquid silicone is an often-mentioned and undesired adverse event. Using small volumes over multiple treatment sessions with the microdroplet technique avoids this problem, as microdroplets of silicone are anchored to the surrounding soft tissue by fibroplasia. However, LIS may track along tissue planes in the path of least resistance when injected in large boluses all at once.

Skin dyschromia is a rare side effect of LIS, occurring most often when too much liquid silicone is inadvertently injected into the dermis. When the inflammatory response to LIS extends into the dermis then post-inflammatory erythema, post-inflammatory hyperpigmentation, and telangiectasia may occur. Often, dermal ridging occurs in conjunction with the dyschromia. Erythema and telangiectasia may be treated with a pulsed dye laser or intense pulsed light device. Hyperpigmentation may be treated with hydroquinone and sun protection. Dermal ridging may improve with intralesional steroid injection, but the response is often incomplete and the problem persistent.

A more concerning potential adverse event to LIS is granuloma formation presenting as edematous, inflamed, indurated nodules or plaques in the subcutis or dermis. Such reactions were described in 2009 by the author with liquid silicone as well as a variety of other permanent or longer lasting fillers such as polymethylmethacrylate and polylactic acid. They are thought to be immune mediated, though the basis of the immune mechanism remains unclear. It has been postulated that granulomatous reactions may be a result of infection at a distant site, as granulomatous reactions to liquid silicone have been noted to appear with the development of acute bacterial dental abscesses or sinusitis, and to resolve upon treatment of the infection. Another theory, proposed by Christensen, is that bacterial biofilm formation around the LIS microdroplet may create a low-grade, chronic infection resulting in an inflammatory host response. Biofilms may occur if bacterial organisms are introduced upon filler injection, or seed the filler later during bacteremic episodes. Once present, they may remain dormant for months or years on foreign body surfaces such as injected liquid silicone. Biofilms may serve as a target of a delayed immune response by the patient when organisms convert back to a planktonic state, explaining the potential for granuloma formation years after injection. In theory, according to Duffy, immune restoration in HIV might also predispose the patient to granuloma formation years later, although evidence does not as of yet support this. It was estimated by Duffy that some fraction of 1% of patients correctly treated with injectable-grade liquid silicone may eventually develop such granulomatous reactions. Should granulomatous reactions develop, they may be treated with high concentrations of intralesional triamcinolone (20–40 mg/mL) at 2–4-week intervals. It should be noted that HIV infection might predispose individuals to adrenal suppression with higher doses of cortisone. In these cases injectable 5-fluorouracil may be beneficial. Based on the biofilm hypothesis, institution of a full-dose, broad-spectrum antibiotic such as minocycline once or twice daily should also occur. Isotretinoin, etanercept, and topical imiquimod have also been used successfully to treat LIS granulomas, in studies by Desai et al, Baumann & Halem, Lloret et al, and Pasternack et 

al. Ultimately, however, granulomas that fail to resolve may require surgical removal.

Conclusion

HPLIS is a safe, effective filler when appropriately employed by experienced injectors using the microdroplet technique. Currently its greatest application is for the permanent correction of HIV-associated facial lipoatrophy, although it is effective for the correction of a variety of facial atrophies and deformities. Injectable liquid silicone has generated controversy in decades past. However, modern, highly purified silicone oils studied in controlled clinical settings have so far proven to be safe agents that warrant distinction. As with any procedure, complications may still occur, and may be more difficult to treat owing to the permanent nature of the product. For this reason, physicians must employ proper injection method and inject only in appropriate patients who have had full disclosure as to the off-label nature of its use and adequate informed consent. Continued studies are ongoing to further examine both long-term safety and efficacy.