Viewpoint 2

Chronic exposure to the ultraviolet (UV) component of solar radiation leads to photoageing which is characterised clinically by fine and coarse wrinkles, dyspigmentation, telangiectasia, laxity, roughness and a sallow appearance (1). Histologically, photoageing is represented by changes in the dermal extracellular matrix including disorganisation and loss of collagen and fibrillin fibrils in the papillary dermis and deposition of dystrophic elastotic material in the reticular dermis (2). The impact of photoageing extends beyond a risk of developing precancerous and cancerous skin lesions and impairs an individual’s psychosocial well-being with anxiety and social isolation as reported consequences (3). Many over-the-counter cosmetic products claim to reduce the clinical signs of photoaged skin; however there is scant evidence from randomized controlled trials (RCTs) to support such claims (4). The use of topical retinoids, including tretinoin, isotretinoin and tazarotene, has been shown in several large RCTs, over the past 20 years, to significantly reduce both the clinical and histological signs of photoageing. Tretinoin emollient cream (0.05% and 0.02%) and tazarotene cream (0.1%) have US Food and Drug Administration approval for the treatment of photoageing. Kligman et al. published the first study of the use of topical tretinoin in the treatment of photoageing (5). Since that time, many placebo-controlled clinical trials have confirmed the ability of topical tretinoin, isotretinoin and tazarotene to repair photoaged skin (6–32). Two large RCTs compared two different retinoids: the first compared tretinoin 0.05% emollient cream and tazarotene 0.01%, 0.025%, 0.05% and 0.1% creams, with vehicle. All retinoid treatment groups demonstrated significant improvements in fine wrinkling as compared with vehicle. Both 0.05% tretinoin emollient cream and 0.1% tazarotene cream led to significant improvement in mottled hyperpigmentation (25). The second trial compared tretinoin 0.05% emollient cream to tazarotene 0.1% cream. The incidence of treatment success, as defined by ≥50% improvement at the study endpoint, was 78% and 67% in the tazarotene group and tretinoin groups respectively. For adverse effects the only significant difference was a higher incidence of skin irritation in the tazarotene group during the first week of treatment (33). The clinical effects of long-term topical retinoid use have been presented in the results of a 24-month RCT of tretinoin 0.05% emollient cream (30). Significant improvements in fine and coarse wrinkling, sallowness, mottled hyperpigmentation and lentigines were noted in the tretinoin treatment group. Use of topical retinoid may be associated with ‘retinoid dermatitis’ which is characterised by local irritation, erythema and desquamation. Side-effects may become less problematic with duration of therapy, or alternatively may be reduced by a more gradual institution of treatment and/or reduced frequency of application. The efficacy of once or three times weekly application of tretinoin emollient cream was evaluated in a long-term extension study of 126 individuals who had already completed 48 weeks of once daily treatment. The benefits obtained from initial daily application were maintained by three times weekly, and to a lesser degree, once weekly application. Of note discontinuing treatment led to some loss of clinical improvement for all variables (21). In many of the more recent studies to investigate the effects of topical retinoids, subjects have also been required to apply sunscreen on a daily basis. Isotretinoin 0.05% combined with sunscreens in a cream formulation used on a once daily basis over a 6 month period produced a significant reduction (P < 0.01) in skin wrinkles as compared with vehicle (29). Furthermore, and intriguingly, regular application of sunscreen alone has been shown to reduce histological signs of solar elastosis (34). The use of photoprotection to prevent signs of photoageing is gaining increasing public interest, with many cosmetic products now containing sunscreen. The regular use of sunscreen should be encouraged in conjunction with ‘sunsmart’ behaviour. Ultraviolet radiation reduces collagen synthesis in the skin accompanied by production of matrix metalloproteinases (MMP). MMP degrade dermal collagen and fibrillin, thereby leading to wrinkling. Studies have shown that application of tretinoin prior to UV exposure can inhibit production of MMP, and thus prevent degradation of collagen (35). Use of topical retinoids induces synthesis of type I collagen in the dermis (16,36). These observations demonstrate the role of retinoids in both preventing and reversing the signs of UV-induced skin ageing. In conclusion, despite the vast array of ‘antiageing’ products now available topical retinoids and sunscreens remain the most tried and tested treatments with long established safety records and proven efficacy in the treatment and prevention of UV-induced skin ageing.