Chapter 2 Photodynamic 2 Photorejuvenation Michael Gold Core Messages Not to be outdone, groups of dermatolo- X gists forged ahead in the cosmetic aesthetic Photodynamic photorejuvenation surgical arena, led by pioneering works in involves the use of a topical photo- dermabrasion and chemical peeling of the sensitizer and a light source. skin. Physicians such as Kromeyer [5], Burks A 20% solution of 5-aminolevu- [6], Harmon and Yarborough [7], and Roe- linic acid and a 20% methyl ester nigk [8] taught us that through the use of dia- cream of 5-aminolevulinic acid are mond fraises or wire brushes, skin rejuvena- the two most commonly used topi- tion was possible. Physicians could produce cal photosensitizers. outstanding cosmetic results when the devic- A variety of visible lasers and non- es were used properly and by skilled clini- laser light sources can be used to cians. Others, such as Brody and Hailey [9], activate the topical photosensitiz- Monheit [10], Coleman and Futrell [11], and er. Rubin [12], among others, laid the foundation Many aspects of photodamage for the use of superfi cial and medium-depth can be treated with photodynamic chemical peeling to cause a controlled wound photorejuvenation. to the skin, with the resultant healing leading to an enhanced cosmetic eff ect. Lasers soon entered into the cosmetic for- ay, and through the early work of Goldman History and Rockwell [13], and Anderson and Parish [14], and others, the term selective photother- Th e fi eld of aesthetic and cosmetic laser sur- molysis became commonplace in many der- gery has been enhanced by some of the out- matologic and aesthetic practices, allowing standing contributions made by many who the clinician to treat an enormous array of paved the way into aesthetic medicine before cosmetic and aesthetic concerns. In the early it was in vogue. Clinicians and researchers 1990s, Goldman et al. [15] described the use such as Kligman et al., who pioneered the ear- of what is now simply known as the IPL, or ly work with topical tretinoin [1] and showed the intense pulsed light device, for the treat- its benefi cial eff ects on the skin surface [2], ment of vascular lesions of the skin. Th is and Voorhees et al. [3], who were the fi rst to broadband wave light source provided physi- describe the eff ects of tretinoin on wrinkles cians with the opportunity to selectively tar- and rhytides of the face have made signifi cant get a variety of concerns within photodam- early contributions. Th ese studies were fol- aged skin, allowing a new era of rejuvenation lowed by those of Van Scott and Yu [4], who treatments to begin. Research quickly spread described the eff ects of alpha hydroxy acids with the use of IPLs, including its expanded and their usefulness in improving skin tex- use into the world of permanent hair removal ture and tone. and pigmented lesion removal. Subsequent 50 Michael Gold work by Goldberg and Cutler [16] and Zelick- provement in their wrinkle appearance. Oth- son et al. (personal communication) showed er important investigations included clinical that, with several IPL treatments, collagen studies by Negishi et al. [22], showing the ef- formation was achieved. Elastin studies dem- fectiveness of IPL photorejuvenation treat- 2 onstrated normalization of dermal structures, ments in the Asian population, and by Her- thus improving the skin’s texture. By adding nandez-Perez [23] showing improvement in all of the benefi ts achieved with IPL, the era of patients of Hispanic ethnicity. “photorejuvenation” was created. Photoreju- IPL photorejuvenation has become a main- venation, no more than an early laser compa- stay in the aesthetic and cosmetic arena; it im- ny marketing tool, quickly became one of the proves both vascular and pigmented con- most commonly performed cosmetic and aes- cerns, and improves the collagen and elastic thetic laser or “light-based” treatments. Th e tissue changes associated with photodamaged reason for this phenomenon was really quite skin. Th e procedure has become predictable simple: IPL therapy led to a global improve- and, in the right hands, with the proper train- ment in patients’ extensive photodamage. ing and guidance, is very safe and eff ective, Vascular damage, manifest by telangectasias with consistent results and minimum down- (pigmented changes, manifest by mottled hy- time. Th e fact that these treatments result in perpigmentation and lentiginous lesions) and minimum downtime for patients is very sig- collagen changes, as seen in histologic analy- nifi cant and is one of the main reasons for its sis, were all improved. popularity today. As a result, the use of IPL Photorejuvenation, as a named procedure has increased tremendously over the past sev- for aesthetic and cosmetic laser surgeons, took eral years, with now almost every laser com- hold when Bitter, in 2000, published the fi rst pany producing an IPL to compliment their clinical manuscript on the topic of photoreju- laser portfolio. IPLs on the market today are venation [17]. In Bitter’s study, more than 90% better than ever, with squared-off pulses and of the patients studied (n=49) had a greater effi cient cooling systems being common fea- than 75% improvement in rosacea symptoms tures of today’s devices. Th e various IPLs cur- (facial erythema and fl ushing), 84% had an rently available are shown in Table 2.1. improvement in their fi ne wrinkles, 78% had IPL photorejuvenation is safe, eff ective, signifi cant changes in their facial pigment, predictable, and is a minimum-downtime and 49% noted an improvement in their pore procedure. Th e success of IPL treatments has size. Each patient in that study received fi ve led to the obvious question. Is it possible to full-face IPL treatments at a 1-month inter- improve on the use of this procedure? A vari- vals. Th is is still the standard of care per- ety of clinical investigators have been ponder- formed today. Others also noted improve- ing these questions for the past several years. ments in photodamage (i.e., photorejuvena- Many believe this can be done through the tion with the IPLs), including several studies use of photodynamic therapy (PDT) to en- by Goldberg, Weiss, and Sadick [18–21]. In the hance the photorejuvenation process. studies by Goldberg [18, 19], one-third of the PDT, in its simplest form, is a procedure individuals (n=30) noted substantial improve- that requires a photosensitizer, light, and oxy- ments with their IPL treatments, while one- gen. Th e most common photosensitizer avail- half of the subjects noted some improvement able for use with PDT is 20% 5-aminolevulin- with the IPL. Weiss et al. [20], in a retrospec- ic acid (ALA). Once applied to the skin, ALA tive analysis of his IPL treated patients, found, is transformed into protoporphyrin IX (PpIX), that at 5 years, patients still maintained im- the active ingredient required for a PDT reac- provement in their skin texture (83%), telan- tion to occur. Previous work has shown that gectasias (82%), and dyschromia (79%). Fur- PpIX is absorbed into actinically damaged thermore, in work reported by Sadick [21], skin cells and into the pilosebaceous units of more than 90% of treated patients had im- the skin. Upon exposure to a light source of a Photodynamic Photorejuvenation Chapter 2 51 Table 2.1. Intense pulsed light sources. IPL Intense initially focused on its use on actinic kerato- pulsed light, FPL fl uorescent pulsed light ses (AKs) and, in the United States, with blue Manufacturer Brand Name light. Blue light was chosen because it coin- cides with the largest absorption band of Adept Medical SpectraPulse PpIX, known as the Soret Band. But this wave- Concepts McCue Ultra Variable length is not the only wavelength that will ac- Pulsed Light™ tivate ALA, and other lasers and light sources, American Omnilight FPL as will be described below, also play key roles Medical Bio Care Novalight FPL in the concept of “photodynamic photoreju- venation” [24]. Candela Ellipse FPL Two ALA photosensitizing products are Cutera CoolGlide Xeo currently on the worldwide market, but only Xeo SA one at present, is on the market in the USA. Genesis Plus Levulan Kerastick is a 20% ALA solution and is manufactured by Dusa Pharmaceuticals Cynosure Cynergy PL (Wilmington, MA, USA). Metvix, as the prod- Cynergy III uct is known in Europe and Australia, and PhotoSilk Plus Metvixia, as the product will be known in the DermaMed USA Quadra Q4 Platinum Series USA, is the 20% methyl ester cream form of ALA, also readily identifi ed as MAL. It is Laserscope Solis manufactured by PhotoCure ASA, Norway Lumenis IPL Quantum SR and is marketed by Galderma (Ft. Worth, TX, VascuLight Elite USA). Each one will be further described be- Lumenis One low. McCue Ultra VPL In the USA, ALA, in the form of Levulan, has been approved by the Food and Drug Ad- MedSurge Prolite II ministration (FDA) for the treatment of non- Advances hyperkeratotic AKs of the face and scalp, uti- Novalis Clareon SR lizing a 14- to 18-h drug incubation followed Solarus SR by exposure to blue light for 16 min 40 s [24]. Pivotal FDA trials have confi rmed the eff ec- Palomar StarLux System tiveness and safety of the product. In phase II MediLux System clinical trials, 39 patients with extensive AKs EsteLux System of the face and scalp were subjected to 16 min Radiancy SkinStation 40 s of blue light aft er a 14- to 18-h ALA drug S P R incubation. Pain associated with the light treatment was common, as was posttreatment Sciton Profi le-MP erythema and edema, which eventually led to Profi le-S BBL a crust formation, lasting up to 1 week.