isolated reports exist of both visual loss and skin necrosis occurring following the application of a range of softtissue fillers to the face, including micronized dermal matrix, bovine collagen, autologous fat, silicone oil, and

15 hyaluronic acid [53, 2, 58, 19, 55, 61]. This is thought to occur from retrograde embolization of the filler leading to occlusion of one of the small terminal arterioles supplying either the adjacent skin or the eye. Although these complications have not yet been specifically reported with periocular filler treatment, visual loss has occurred following injections into the glabella region [2]. The latter remains a particular concern in the periorbital region because the palpebral and anterior orbital vasculature is derived from the same source as that supplying the globe itself (i.e., the ophthalmic artery). The risk of embolization in general can be minimized by slow injection of the filler and deep pre-periosteal placement.

Orbital hemorrhage and globe trauma from injection are both additional potential causes of visual loss associated with these treatments. Consequently, all sighted patients receiving orbital or periorbital volume augmentation with soft-tissue fillers should have their visual acuity checked preoperatively and be consented for the theoretical risk of visual loss. Other significant potential complications include infection and diplopia.

15.4 Types of Injectable Soft-Tissue Filler

15.4.1Collagen Fillers

Soft-tissue fillers composed of bovine collagen were the first to be first introduced, in the late 1970s, in the form of Zyderm® and Zyplast® (Allergan, Irvine, California) [38]. However, problems with allogenicity, requiring patients to undertake a pretreatment allergy test, limited their popularity. Bioengineered human dermis products Cosmo Derm® and CosmoPlast® (Inamed Division of Allergan, Santa Barbara, California) were approved by the US Food and Drug Administration (FDA) in March 2003 and do not require such testing before use. Other collagen products include Cymetra®, composed of micronized human cadaveric dermis (AlloDerm, LifeCell Corporation, Palo Alto, California) and Fascian®, composed of injectable human cadaveric fascia (Biosystems, Beverly Hills, California). These products, however, have reportedly had problems with inaccurate filler placement and lumpiness [23].

15.4.2Hyaluronic acid Fillers

The second major group of soft-tissue fillers are those composed of hyaluronic acid, derived from either animal

or bacterial sources. Hyaluronic acid was proposed for use as a soft-tissue filler because it is a component of skin, with structural, elastic, and hydrating properties, but was initially limited by its rapid degradation in biological tissues [3]. However, cross-linking was later found to stabilize it, prolonging its tissue duration time to over six months [51].

The first such stabilized hyaluronic acid filler to gain FDA approval was Restylane® (Medicis,Scottsdale,Arizona) in December 2003. Since then a wide range of other hyaluronic acid products have become available, each with slight di erences, relating to the source derivation (animal versus bacterial), the method and amount of cross-linking, and the particle size [12, 23]. The latter is particularly important as a larger particle size will increase viscosity, reduce ease of injection and increase duration of the filler. In general, more viscous fillers are reserved for deeper softtissue augmentation and require larger cannulas for injection with increased associated patient discomfort.However, they have the advantage of more defined contouring and increased longevity. Some of the most commonly used examples of hyaluronic acid fillers include Restylane Lipp®, Restylane Fine Line®, Restylane Touch®, Restylane Vittal®, Restylane®, Restylane Perlane® and Restylane SubQ® (Medicis and Q-med, Uppsala, Sweden); Juvederm®, Juvederm Ultra® and Juvederm Ultra Plus® (Allergan, Irvine, California); Captique® (Genzyme, Framingham, Massachusets and Allergan); HydraFill® (Allergan), Purogen® (Mentor, Santa Barbara, California) and the animal derived Hylaform® and Hylaform plus® (Genzyme, and Allergan) [12, 23]. Nonanimal stabilized hyaluronic acid fillers are commonly termed NASHA fillers.

Hyaluronic acid fillers have the advantage over collagen fillers of instant reversibility with the application of hyaluronidase. The latter is a cheap, readily available product which can be easily injected into the treated area. In addition, collagen fillers are contra-indicated in people with a known allergy to bovine collagen, pregnant or breast feeding women, or patients with connective tissue disorders. However, it has been suggested that collagen fillers may o er superior results to hyaluronic acid fillers when treating very superficial areas [23].

15.4.3Semipermanent Injectable Soft-Tissue Fillers

In addition to the two principal categories of injectable soft-tissue fillers outlined above, there are a few isolated, longer lasting, semipermanent products that have been approved for deep tissue augmentation [6]. These include poly-L-lactic acid (Sculptra®, Dermik Labs, Bridgewater, New Jersey), which currently has approval from the FDA for use in patients with HIV-therapy-induced facial