Approach
Treatment is guided by the age and skin type, texture, and thickness of the skin of the patient, as well as by the degree of photoaging, severity of the wrinkles, and presence of gravitational changes. In addition, the expectations and lifestyle of the patient must be taken into consideration.
Treatment options range from the topical application of creams, chemical peels, neurotoxins, and fillers, to laser treatments, and surgery. Chemical peels of various depths can be used to rejuvenate the skin, and the depth chosen depends on the location and severity of the wrinkles. The minimization of aggravating factors, such as abstinence from smoking, appropriate sun protection, and the use of a high sun protection factor (SPF) sunscreen, also plays a crucial role.
No obvious wrinkles at rest or on animation
Noninvasive treatment is recommended for these patients, with most young adults in this category benefiting from the combined therapeutic use of topical retinoids, antioxidants, and superficial chemical peels available over the counter. Of these therapies, topical retinoids are the most efficacious for wrinkle prevention and treatment.
Topical retinoids
These vitamin A derivatives lead to improvement in the appearance of fine wrinkling and actinic keratoses, as well as reduced roughness and hyperpigmentation. They work by stimulating exfoliation of epidermal cells; repairing DNA damage, dermal collagen, and small blood vessels; shrinking sebaceous glands leading to reduced pore size and skin tightening; and providing new collagen and a new, thicker epidermis.[44][45]
Tretinoin is the most effective retinoid for the treatment of photodamage.[46][47][48] It works most effectively when applied continuously over long periods and at night.
Isotretinoin is effective in improving the appearance of both coarse and fine wrinkles, with less reported irritancy.[49]
Retinaldehyde has also been found to be effective in improving the appearance of skin wrinkling.[50]
Tazarotene, initially developed for the treatment of plaque psoriasis, results in continued improvement in the appearance of fine and coarse wrinkling, hyperpigmentation, surface roughness, and global severity of photoaging.[51] It is believed to be as efficacious in alleviating wrinkles as tretinoin.
Adapalene, a retinoid-like drug normally indicated for acne, is also effective for the treatment of photoaging.[52]
Antioxidants
These agents include green tea, vitamins C and E, and coenzyme Q10, and come in a cream, lotion, or oral formulation.
Work by neutralizing free radicals produced by the sun, stress, and pollution.
Superficial chemical peels
A small number of over-the-counter superficial chemical peels, such as low pH soaps, can be used to give the skin a more rejuvenated appearance.
Chemical peels improve the appearance of the skin, and various peeling agents exist. Alpha-hydroxy acids, derived from fruits and vegetables, increase epidermal and collagen thickness, as well as epidermal and dermal hyaluronic acid levels.[53] Complications are mild, and include dryness and mild irritation. Salicylic acid (30%) in a hydroethanolic vehicle is also used for superficial peels.[54]
Repeated in a series of three to five chemical peels at monthly intervals, with the maximum treatment effect lasting between 6 and 12 months.
Superficial wrinkles on animation only
These patients may be treated with topical retinoids, antioxidants, superficial chemical peels, and botulinum toxin (BTX) injections. These treatments can be given in succession, with the topical application of retinoids and antioxidants preparing the skin for the superficial chemical peel. Following the peel, complete restoration of the skin must precede BTX injections.
BTX
Injection of this neurotoxin temporarily inhibits muscular contraction, thus rejuvenating the wrinkled face by reducing the hyperkinetic lines of facial expression. Serotypes A (e.g., abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA, prabotulinumtoxinA) and B (e.g., rimabotulinumtoxinB) have demonstrated clinical use.[55] Serotype A is the most commonly used serotype and represents the first-choice treatment given that several randomized trials have shown efficacy, the optimal dosing, and safety. It is used to reduce lines and furrows, particularly "crow's feet", glabellar lines, bunny lines, perioral wrinkles, platysmal bands, and horizontal forehead lines caused by dynamic muscular activity.[55][56][57][58] There are no comparative studies available between the different formulations of serotype A, and there is no indication of which works better in specific anatomical areas. Although rimabotulinumtoxinB has been used in the treatment of hyperkinetic facial lines, there are fewer data regarding the efficacy and optimum doses of this serotype.[59]
Advanced techniques for use by experienced physicians include injection into muscles of the lower face and neck.[60][61]
Treatment effects can persist for 3 to 6 months, after which treatment has to be repeated. The most common adverse events are injection-site pain, bruising, headache, short-term hypoesthesia, and blepharoptosis.[62][63]
Deep wrinkles on animation only
For patients in this category, BTX injections are the treatment of choice and represent the first-line therapy followed by medium-depth peels, fillers, dermabrasion, and laser ablation.
Medium-to-deep thickness chemical peels
Ameliorate superficial wrinkles and pigmentary changes; deep-thickness peels are used for the treatment of deep wrinkles.[64][65]
Trichloroacetic acid (TCA) (acid concentration 30% to 40%) alone or in combination with other substances (Jessner solution: resorcinol 14 g, salicylic acid 14 g, lactic acid 14 mL in ethanol to make 100 mL) is the first-choice chemical peel and results in a medium-depth peel.[66] Adverse effects include milia formation, herpes labialis, postinflammatory hyper- or hypopigmentation, and scarring.
Pyruvic acid is converted to lactic acid, resulting in a medium-depth peel. It improves skin texture, and the appearance of fine wrinkling and hyperpigmentation.[67]
A phenol peel results in a deep-thickness peel. It is associated with postpeel edema and necrosis, and has longer recovery times.[68] Appropriate analgesia, cardiac monitoring, and resuscitation equipment are necessary because of the risk of cardiac arrhythmias and laryngeal edema. This agent is therefore used as a last-line therapy.[69]
Medium-depth and deep-thickness peels are usually not repeated as a series.
Fillers
These agents restore facial fullness and contribute to soft-tissue augmentation as a means of improving the appearance of contour defects associated with aging. Dozens of filling agents exist. They can be classified according to their duration of effect into temporary or biodegradable agents (collagen, hyaluronic acid, autologous fat), semipermanent agents (calcium hydroxylapatite, poly-L-lactic acid), and permanent agents (polymethylmethacrylate (PMMA), silicone).
Facial fillers can be either replacement agents, which occupy space in the deep dermis or subcutaneous fat, or stimulatory fillers, which stimulate fibroblast activity, collagen synthesis, and soft-tissue growth. The level of injection depends on the area treated and the type of filler used. Fine wrinkles are treated with intradermal fillers and deep folds with agents injected into the deep dermis or subcutaneous tissue.
Hyaluronic acid products are temporary fillers, and are the most commonly used because their unique viscoelastic properties and high water-retention capacity fill grooves effectively. Depending on the chemical nature of the material of the hyaluronic acid, they can be injected with different techniques.[70] They are relatively free of adverse effects, but carry a very small risk of allergic reactions. Results last for 6 to 12 months.[71][72][73]
Poly-L-lactic acid is a biodegradable, semipermanent filler injected into the deep dermis or subdermally. It can cause granuloma formation. It can be used for the correction of facial wrinkles and nasolabial fold wrinkles, and the treatment of facial lipoatrophy. Results can last up to 25 months. However, it can cause granuloma formation.[74][75][76][77]
Collagen as a filling agent may be bovine, human, or porcine. Bovine collagen, the first product approved for soft-tissue augmentation, requires skin testing before injection to rule out allergy; however, human-derived products do not require skin testing.[78] Results can last 3 to 18 months.
PMMA can be suspended with bovine collagen or hyaluronic acid. It is used to treat deep wrinkles and has a long-lasting effect, but is associated with permanent granuloma formation.[79] Although the incidence of this adverse reaction is debated, the risk of granuloma formation has made this filler less popular.
Autologous fat as a filling agent has the advantage of lacking immunoreactivity and can be used in large volumes, but has the disadvantage that it requires fat extraction before injection.[80]
Calcium hydroxylapatite is a semipermanent filler that does not require skin testing. Adverse effects include erythema, edema, transient lumpiness, and granuloma formation.[81][82][83][84] Results may last beyond 1 year.
Silicone is a permanent filler, injected into the deep dermis or subdermally. Although used in the past, it is no longer recommended for facial volume because of the high risk of granuloma formation and silicone migration.
Superficial wrinkles at rest, deep wrinkles on animation
The treatment approach for these patients is essentially the same as for those with deep wrinkles on animation only. However, all procedures have to reach deeper layers of the skin. Although medium-to-deep thickness chemical peels, BTX injections, and fillers may be beneficial, more invasive treatments such as dermabrasion and skin resurfacing using laser ablation are normally indicated. Dermabrasion and laser ablation results continue to improve for up to 18 months as collagen remodeling takes place. Dermabrasion or microdermabrasion represent the first-line treatment followed by fractional photothermolysis or laser ablation.
Dermabrasion
This technique is indicated for treating superficial wrinkles, either at rest or on animation. Although less popular, it is still an effective resurfacing procedure, mostly useful for lines of the perioral region.[85] It is an inexpensive and simple procedure performed under local anesthesia or a regional nerve block. Using a hand-held dermabrader, the epidermis and upper layers of the dermis are mechanically removed, resulting in lowering and smoothening of the abraded creases. Ablation is usually extended down to the level of the mid-dermis at the papillary-reticular junction.[86] Re-epithelialization of this partial-thickness injury is usually completed within 7 to 10 days. Incomplete dermal regeneration and neocollagen formation have been demonstrated following dermabrasion.
Although associated with less erythema and hypopigmentation than other techniques, post-treatment complications may occur, including scarring, hyperpigmentation, and reactivation of a herpes virus infection. The effectiveness of the technique and the risk of complications are related to the depth of injury, with deeper treatments associated with higher complication rates. For persistent or deeper wrinkles, dermabrasion may be repeated 6 to 12 months after the initial operative session.
Microdermabrasion
Superficial wrinkles and photoaged skin may be treated by microdermabrasion, where crystals or other abrasive substances are blown onto the face.[87] The mechanism of action of this technique is not clear. Although actual skin abrasion has not been demonstrated, histologic changes in the reticular dermis (namely, vascular changes) have been reported.[88] Beneficial effects of microdermabrasion include a reduction in skin stiffness, and an increase in cutaneous compliance, as well as a mild improvement in the appearance of photodamaged skin.
Fractional photothermolysis
Laser ablation
Ablation, which refers to the removal of the epidermis and upper dermal layers, is widely used in the treatment of fine wrinkles visible at rest and/or on animation. The laser modalities indicated for facial rejuvenation are the ultrapulse or scanned CO₂ laser and the Er:YAG (erbium:yttrium aluminum garnet) laser. The choice of laser used is dependent on the experience of the surgeon and the availability of the laser. The energy emitted by the laser is absorbed by water in the skin surface, which is known as the primary target chromophore. Thus, a controlled thermal injury is initiated and tissue vaporization occurs, followed by coagulation.[86] Changes in skin texture and improvement in the appearance of wrinkles result from superficial skin ablation and tissue shrinkage secondary to heat-induced remodeling and collagen contraction.[92]
CO₂ lasers penetrate deeper into the skin and lead to a greater inflammatory reaction, prolonged erythema, and longer-lasting results, but there is also an increased risk of hypopigmentation and scarring.[93] Er:YAG lasers have an increased affinity for water-containing tissues and a lower depth of penetration.[94] As a result, compared with CO₂ lasers, less thermal damage occurs per pass, and less tissue contraction, but more intraoperative bleeding occurs. However, decreased postoperative morbidity with a shorter recovery period and fewer complications are also recorded. Postoperative morbidity mainly depends on the depth of the thermal injury. Longer-pulse width Er:YAG lasers penetrate deeper, leading to the desired ablation and tissue contraction with greater control than CO₂ lasers.
Before the initiation of laser therapy, a preoperative evaluation of the patient, taking into consideration the skin quality and type, as well as the location and thickness of the wrinkles, should be undertaken. The two primary areas where laser rejuvenation has been shown to be successful are the perioral and periorbital regions. Fine static wrinkles respond better to laser treatment than hyperdynamic facial creases. For dynamic lines, additional modalities such as BTX or fillers may be more useful.
Moderate to severe photodamage shows best results with the use of a CO₂ laser. Excellent results can be achieved using an Er:YAG laser to treat more superficial wrinkles and less photodamaged skin.[95] Combination CO₂ and Er:YAG lasers allow sufficient tissue ablation while being associated with safer thermal stimulation and coagulation.
Deep wrinkles and sagging skin at rest and deeper wrinkles on animation
These patients are best served with the combination of a surgical procedure (autologous fat grafting or rhytidectomy) and a local treatment (microdermabrasion, dermabrasion, or laser ablation) to improve the appearance of visible folds.
Autologous fat grafting
This technique has become popular because volume loss has been recognized as one of the primary components of the aging process.[96] Facial lipofilling is being widely used for volume replacement in aesthetic surgery and in facial rejuvenation.[97] Among facial areas, the malar region is particularly suited to volume augmentation with fat transplantation. Fat injections have also been successfully used for nasolabial folds attributable to soft-tissue atrophy, where treatment should include the release of the dermal attachments creating the folds. Less favorable results have been reported for the effacement of glabellar creases. Structural fat grafting has also been reported to be beneficial in rejuvenation of the dorsum of the hand.[98]
Fat is harvested from the abdomen and medial thighs by liposuction using small-diameter blunt-tip cannulas. After centrifuge, fatty tissue parcels are placed separated from each other in the desired locations. The survival of fat grafts is dependent on the technique used to harvest, refine, and transfer the adipose tissue. The most challenging part of the procedure is placing the fat in small aliquots injected into multiple subcutaneous planes.[99] To obtain predictable results, most of the oil and blood should be removed. Minimal overcorrection of <10% should be performed. When fat grafting is performed in conjunction with a lifting procedure, it is not recommended to carry out the facelift dissection across the areas that will be grafted so as to enhance revascularization of the fat grafts.[100]
The most frequent complications are irregularities and contour defects, due to inappropriate fat harvesting and/or the lipofilling injection techniques.[101] Results may be related to the age of the patient given that more favorable results have been reported in younger (<40 years) than in older (>60 years) patients.[100]
Rhytidectomy (facelift)
For patients presenting with sagging skin and deep folds attributable to gravitational descent, a facelift or rhytidectomy procedure is indicated. Although patients with fine wrinkles and severely photodamaged skin are unfavorable candidates for such aesthetic surgery, rhytidectomy is considered by some surgeons to be the most beneficial treatment of facial-aging in most people over 40 years of age.[102]
Techniques differ depending on the plane of dissection and the type of placation, or on the suspension of the underlying tissues of the face and neck. They include subcutaneous lifting, SMAS (superficial musculoaponeurotic system) techniques, the MACS (minimal access cranial suspension) lift, and the subperiosteal facelift. Deep plane and composite rhytidectomies achieve some improvement in the appearance of the nasolabial folds.[103] Forehead plasties, performed either endoscopically or using the coronal approach, elevate the ptotic eyebrows and may smooth the transverse forehead and/or glabellar lines.[104] Tightening of the skin and suspension of the subcutaneous structures provided by a facialplasty offer some improvement to the appearance of overhanging folds and gravitational lines. It should be made clear to patients that facelifts address only ptosis and have no effect on wrinkles and skin texture.
Facelifts are associated with the risk of scarring, hematoma formation, alopecia, nerve damage, facial asymmetries, and facial nerve palsy. Results can last for up to 15 years.
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