Trattamento con Laser Frazionato Non Ablativo

Fractional Nonablative Palomar 1540 Smagliature

Fractional Nonablative 1540-nm Laser Treatment of Striae Distensae in Fitzpatrick Skin Types II to IV: Clinical and Histological Results

Francesca de Angelis, MD; Larissa Kolesnikova, MD; Franco Renato, MD; and Giuseppina Liguori, PhD.

Abstract
Background: Current striae treatments in their ability to deliver long-lasting improvements for all skin types. The success of fractional nonablative lasers for surgical scars has been attributed to the controlled wound-healing response stimulated by microscopic columns of epidermal and dermal thermal damage.
Objectives: The authors describe the safety and efficacy results of treatment with a fractional nonablative 1540-nm erbium:glass laser in patients with Fitzpatrick skin types II to IV for both striae rubra and striae alba.
Methods: A 51-person clinical study was Conducted on striae ranging in duration from one to 40 years. Nine different anatomical locations were treated, including the breasts, hips, and abdomen. Treatment parameters included two to three passes with the 1540-nm laser, with energy settings from 35 to 55 mJ/mb with the 10-mm optical tip or 12 to 14 mJ/mb with the 15-mm optical tip. Two to four total treatments were performed at four- to six-week intervals. Nonblinded efficacy evaluations were performed on all 51 patients; blinded evaluations were conducted by three independent clinicians on 14 randomized sets of pre- and post-treatment images on a 0% to 100% quartile improvement scale. Skin reactions were assessed by the treating physician and recorded at multiple time points, and histology was conducted with hemotoxylin and eosin as well as Orcein-Giemsa staining.
Results: Nonblinded clinical assessments rated overall improvement as 50% or greater for all patients at six months or longer after the last treatment. Blinded evaluators reported an overall mean improvement score of 51% to 75% on properly selected images taken at least three months after treatment (n = 11). In all patients examined at either 18 or 24 months after treatment there was no recurrence of striae. Typical side effects included transient erythema and edema. A small minority of patients experienced transient cases of trace postinflammatory hyperpigmentation (PIH), which all resolved. Histologic observations showed thickening of the epidermis and dermis, neocollagenesis, and increased elastin deposition one month after the last treatment.
Conclusions: Positive safety and efficacy results with the fractional nonablative 1540-nm erbium:glass laser for the treatment of striae rubra and striae alba ranging in maturation age from one to 40  years was demonstrated
in Fitzpatrick skin types II to IV.

Keywords
striae, stretch marks, fractional lasers, nonablative lasers, cosmetic medicine

Accepted for publication July 17, 2010.
 

Striae distensae, or stretch marks, arise from progressive or rapid stretching of the dermisl and generally form following rapid weight changes during adolescent growth spurts, corticosteroid use or pregnancy and (less typically) due to Cushing syndrome.2-4 The classic anatomical sites affected include the abdomen and breasts for pregnancy related striae, the outer thighs or lumbosacral regions for adoles¬cent boys, and the buttocks, thighs, upper arms, and breasts for adolescent girls.5,6
Striae progress through three different stages of matura¬tion: the acute stage is characterized by red and slightly raised striae (rubra), the subacute stage is characterized by purpuric striae, and the chronic stage is characterized by hypopigmented and atrophic striae (alba).7
Dr. de Angelis is a plastic surgeon in private practice in Naples, Italy.
Dr. Kolesnikova is a dermatologist in private practice in Milan, Italy.
Drs. Renato and Liguori are from the Pathology Department of the G. Pascale National Cancer Institute, Naples, Italy.

Corresponding Author:
Francesca de Angelis, via A.D'Antona 20, 80131, Naples, Italy. E-mail: francesca.deangelis@yahoo.com

METHODS
Laser Device
The 1540-nm fractional nonablative Er:Glass laser (Lux1540) was developed as an accessory to the StarLux Laser and Pulsed Light System (Palomar Medical Technologies, Inc.). The laser generates an array of focused microbeams, up to 470 per pulse. The system's two interchangeable optical tips allow a spot size of either 10 mm and 15 mm delivering ener¬gies up to 70 mJ/µb and 15 mJ/µb, respectively. Corresponding densities are 100 mB/cm2 per pulse with the the 10-mm tip and 320 mB/cm2 per pulse with the 15-mm tip.

Safety Evaluations
Side effects were evaluated by the treating physicians immediately after treatment, prior to the next treatment (four to six weeks), and at three, six, and 12 months after the final treatment for long-term evaluations. All side effects were graded for severity and followed until resolution.

RESLULTS
Patient ages ranged from 13 to 56 years,(mean, 33 years). Fitzpatrick skin type ranged from II to IV (Table 2). The duration of striae ranged from one to 40 years, with an average duration of 12 years (Table 3). The striae formed as a result of pubertal growth (41%, n = 21), pregnancy (31%, n = 16), weight change (20%, n = 10), muscular atrophy (2%, n = one), or unknown causes (6%, n = three) (Table 4).

Histology
H&E staining of pretreatment tissue samples revealed an atrophied epidermis and flattened rete ridges within the papillary dermis. No intact collagen fibers were identifi¬able in the striae before treatment, and the degenerated appearance of the fibers resulted in uneven staining as well as indistinct borders (Figure 1A). In contrast, following three 1540-nm treatments with the 10-mm tip at 40 mJ and 10-ms pulse width, significant neocollagen¬esis was observed (Figure 1B). Elastic fibers in the reticular dermis appeared sparse and fragmented prior to the 1540-nm treatment (Figure 2A). One month after the third treatment, elastic fibers were uniformly increased in number throughout the reticular dermis (Figure 2B).

Safety
Treatments were well-tolerated, with only minimal side effects. Immediately following treatment, all patients experienced the expected side effects, of edema and/or erythema, with the majority of cases resolving within two to seven days or shortly thereafter. In general, the severity of the side effects depended on the energy level setting. For energy settings between 20 and 30 mJ/µb, mild edema and/or erythema was initially observed and resolved between six and 12 hours. For energy settings between 30 and 40 mJ/µb, edema typically resolved within six to 24 hours, and erythema resolved within seven days. For energy settings between 40 and 50 mJ/µb, edema typically resolved within ,24 hours, and erythema resolved within two weeks. Mild PIH was observed in eight patients, but cases were trace or mild in severity, and the majority resolved within one to four months. The remaining three case resolved by seven, 11, and 15 months after treatment, but we feel it is likely that these cases may have resolved earlier since they were not evaluated until later follow-up visits. The onset and duration of PIH were largely dependent on the patient's Fitzpatrick skin type, as well as strict adherence to proper sun exposure precautions (use of sunblock and no direct sun exposure). There were no reports of hypopigmentation, burns, blisters, or scars at any time throughout the study.

Table 2. Fitzpatrick Skin Type

Efficacy
Nonblinded study investigators observed improvements of 50% or greater in the appearance of striae for all 51 study patients. These results were corroborated in a blinded review conducted by three independent physicians on a subset of 14 images from these 51 patients; for all correctly selected images (n = 11), blinded reviewers reported an overall mean improvement score of "3," or 51% to 75%. "Correctly selected" images included those selected in which the photos accurately reflected the clinical condition of the striae and in which the pre- and post-treatment views were accurately matched.
Overall, the fractional nonablative 1540-nm laser treatment was found to be effective for a wide range of striae varying in color (rubra to alba), anatomical location (breasts, hips, abdomen, thighs, flanks, etc), and matura¬tion (one to 40 years). Examples of clinical benefits achieved in variously-aged striae and in various Fitzpatrick skin types are shown in Figures 3 through 6.
The histologic and clinical results of this study demon¬strate the safety and efficacy of the fractional nonablative 1540-nm Er:Glass laser for the treatment of a wide range of striae distensae, from early rubra to late alba stage. Treatments were well tolerated With only minimal (and expected) side effects, all of which resolved. As of the writing of this report, half of the participants had been followed for up to 18 months post-treatment, and half had been followed for up to 24 months with no recurrence of striae in either group.

Discussion
Our selection of the fractional nonablative 1540-nm laser device applied in this study was based on its demonstrated efficacy in the treatment of scars as well as its preservation of the stratum corneum for enhanced safety and expedited skin recovery after treatment.34 Fractional nonablative lasers deliver microcolumns of thermal damage deep into
the epidermis and dermis to stimulate a controlled wound- healing response, which in turn results in remodeling and regeneration of dermal collagen.7,25,37
Although a variety of previous therapies have been used to treat striae distensae, no previous medium has resulted in sustainable results for both pigment and textural irregulari¬ties with equivalent efficacy for striae rubra and striae alba.37 Topical applications of glycolic acid and ascorbic acid have yielded variable results,38,39 and tretinoin therapy appears to be beneficial only for early-stage striae (rubra).11,12 Studies with 585-nm PDL technology demonstrated pigment correc¬tion for striae rubra but not for striae alba, a difference attrib¬uted to the system's blood vessel-selective wavelength. Conversely, better outcomes for striae alba were observed in a recent 1550-nn study.37

Blinded evaluators in our study observed improve¬ments of between 51% and 75% for 11 of 14 correctly selected images of treated striae, including striae rubra and alba. Nonblinded assessments of the entire population by study investigators concluded that all striae exhibited improvements of 50% or greater. One of the strengths of this study was the wide diversity in striae maturation, as shown in Table 2. Although most striae fell between the ages of three and 20 years (72% total), 14% of treated striae scars were one to two years old, and 14% were more than 20 years old, The observed corrections for pigmented striae can most likely be attributed to the extrusion of melanin through microscopic epidermal necrotic debris (MENDs), along with the migration of nearby keratinoc¬ytes and melanocytes from adjacent untreated tissue into coagulated tissue.25,34
Histologic analyses have demonstrated that striae formation parallels the wound healing observed in scar formation9; therefore, comprehensive improvements should address the underlying texture and scarring seque¬lae. Preliminary investigations of fractional nonablative photothermolysis demonstrated the capability of this technology to induce dermal remodeling,'" and these histologic changes (neocollagenesis, increased epidermal thickness) have recently been confirmed in striae studies with the 1550-nm laser.7,37
The dermal remodeling capabilities of the fractional nonablative 1540-nm laser were recently tested in a resurfacing scar study conducted by Vasily et al,34 in which 73% of treated scars improved 50% or more, and histologic observations included renewal and reorganization of dermal collagen. In the current study, we observed thickening of the epidermis and dermis as well as greater organization and an increased number of collagen fibers at 30 days after the last treatment. Additionally, we observed increased numbers and more uniform distribution of elas¬tic fibers in the papillary dermis. These results, although suggestive of enhanced rebuilding of dermal elastin, were taken from only a small number of patients and will require additional sampling to confirm. If validated with larger systematic sampling, these findings support the rebuilding of skin as an important mechanism leading to the observed improvements in the appearance of striae.

As mentioned previously, independent blinded image evaluations from this study revealed improvements of 51% to 75% or more in the appearance of striae. In contrast blinded evaluators in the Bak et a137 study reported a mean clinical improvement of 25% to 50% with a 1550-nm laser with the majority graded as improving less than 25%. Of the eight patients randomly evaluated in a study with the 1550-nm laser by Stotland et a1,35 63% of patients demonstrated improvements of 26% to 50%. Although the litmus test would be a direct-comparison, split-body study of both fractional nonablative devices, we speculate that the higher efficacy of the 1540-nm device in our study may be attributed to the following three factors: (1) the pre- and post-treatment topical treatment regimen, (2) the optimized zone of treatment established through our range-finding testing, and (3) the mode in which the treatment was applied.
We feel that the topical treatment regimen kept the skin well-hydrated and prevented or managed any postinflammatory pigmentation, particularly for patients with darker skin types. Although there is a precedent for topical applications of 10% Lascorbic acid (a form of vitamin C) provid¬ing some improvement for striae alba in combination with 20% glycolic acid,38 since there are no published reports of either hydrocortisone or hydroquinone independently improving striae, we feel any bias introduced with the application of this topical regimen would be minimal.
Our optimized zone of treatment was developed to allow for the best combination of coverage and depth of treatment. Treatments that yield high coverage rates or deep dermal penetration increase the risk of prolonged side effects; conversely, shallow coverage or treatments with limited dermal depth are associated with lower effi¬cacy. Among the authors practices, enough patients (more than 100) have been treated to identify a standard treatment protocol associated with long-lasting results and limited side effects. By first applying a range of treatment parameters and closely monitoring our patients for both safety and efficacy outcomes, we were able to determine that treatment parameters ranging from 30 to 50 mJ/µb provided the best clinical outcomes with only limited or transient side effects. Finally, we speculate that the stamping mode of energy delivery may be better suited to addressing the unique textural irregularities of striae due to the practitioner's ability to compress the skin for uniform, even contact, which ensures effective and consistent distribution of microbeams into the skin.
Another pitfall of many current striae treatments is their inability to provide long-lasting results. Current published studies either fail to mention the longevity of observed improvements or state that their results require periodic maintenance treatments 714 We have now followed-up with half of our patients for up to 18 months and the other half for up to 24 months posttreatment and observed no recurrence of striae.
Patients tolerated the treatment well, and all observed side effects were transient in nature. Side effects reported immediately following treatment included erythema and edema, which typically resolved within two to seven days. Trace PIH was observed in a small majority of patients and resolved over time These skin reactions are characteristic of fractional nonablative treatments and are indicative of dermal wound healing.
The limitations of our study include the small set of images available for blinded review due to the challenges of obtaining reproducible pre- and posttreatment images of striae. Striae are particularly difficult to photograph, requiring reproducible lighting and subject positioning. As a result, we only selected those images that accurately reflected the clinical condition of the striae. We also learned that proper patient selection was critical to ensuring that striae responded quickly and effectively to treat¬ment. Slower improvement was observed in darker skin types (IV-V), with maximal improvement often not visible until a year after the final treatment due to the lower energy settings, which helped avoid side effects such as hyperpigmentation. Another limitation is the lack of a universal classification scale to grade the condition of striae prior to treatment. Ideally, such a scale could be applied to guide the physician in designing the optimal protocol (ie, number of treatments and follow-up visits) and would provide the physician with an expected time-frame for when maximal results would be achieved.
Based on our experience, improvements in striae may be affected by sex, age, body contour sites, skin tone, diet, age of striae, etiology, and striae pattern. Body locations that seemed to respond better to treatment included the abdomen, breast, inner thighs, and legs, whereas striae located on the buttocks and outer thighs seemed to be associated with an increased risk of hyperpigmentation. As stated, we have now treated striae ranging in matura¬tion age from one to 40 years and feel that the improve¬ments are more dependent on the density, length, and depth of the striae than on maturation age.

CONCLUSIONS
Significant textural and pigment corrections were observed for a wide range of striae rubra and striae alba after treatment with a 1540-nm fractional nonablative laser. Advantages of the fractional technology include greater preservation of the stratum corneum for enhanced safety, along with dermal remodeling through controlled wound healing. Side effects were minimal and resolved relatively quickly. High rates of clinical efficacy (as evaluated through independent blinded review as well as physician assessment) were reported. Histologic studies showed neocollagenesis, epidermal thickening, and increased elastic fibers.
Disclosures
Dr. de Angelis is a paid investigator and speaker for Palomar Medical (the manufacturer of the laser used in this study).
Funding
Palomar Medical (the manufacturer of the laser used in this study) provided writing assistance for this manuscript.

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