Treatment Effects of Combined Radio-Frequency Current and a 900 nm Diode Laser on Leg Blood Vessels

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1 Lasers in Surgery and Medicine 38: (00) Treatment Effects of Combined Radio-Frequency Current and a 900 nm Diode Laser on Leg Blood Vessels Mario A. Trelles, MD, PhD, 1 * Manuel Martín-Vázquez, PhD, Oswaldo R. Trelles, PhD, and Serge R. Mordon, PhD 3 1 Instituto Médico Vilafortuny/Fundación Antoni de Gimbernat, Cambrils, Tarragona, Spain Computer Architecture Department, University of Málaga, Málaga, Spain 3 INSERM IFR 114, Lille University Hospital, Lille, France Background and Objectives: Effective laser treatment of leg veins remains a major challenge. The present study examined the safety and efficacy of a new technology for leg vein treatment combining 900 nm diode laser with radiofrequency (RF) current. Study Design/Materials and Methods: Forty patients, skin types II IV, received a maximum of three treatments on 1 4 mm leg veins at -week intervals with a 900 nm diode laser (50 millisecond exposure time, average fluence 0 J/cm ) and RF (energy 100 J/cm 3 ). Results were assessed after each treatment and at and after the final session. Patients rated their satisfaction with the clinical outcome on a five-item scale. Clinician and computer analysis of the clinical photography was also performed, in addition to histological assessment. Results: One or two sessions were required in the majority of patients. Shortly after treatment, histology revealed contracted vessels with perivascular edema. Side effects were extremely rare. The clinician - and -month assessments showed that 70% and 8.5% of subjects, respectively, achieved over 50% clearance, with patient and computer assessments lower and slightly higher, respectively. Treatments showed greater efficacy on thicker vessels and in the darker skin types. Conclusions: The success of the treatment, minimal side effects, and patient comfort suggest that this combination is an effective, safe technique for leg vein treatment. When compared to previous studies using diode laser alone, the very low fluence needed to achieve vessel clearance emphasizes the role of RF energy. Lasers Surg. Med. 38: , 00. ß 00 Wiley-Liss, Inc. Key words: electrical current; ELOS; laser; leg vein; radiofrequency; vascular lesions INTRODUCTION Despite developments in laser technology and treatment techniques, the laser treatment of leg veins remains a major challenge in aesthetic medicine. The main difficulties in treating these lesions are the large variation in skin pigmentation, and the location, size, and depth of the blood vessels. Each of these factors demands different specifications for the laser system chosen for treatment, including wavelength, pulse duration, and spot size. The presence of biological pigments in the skin reduces the penetration of visible light lasers and the visible component of intense pulsed light (IPL) systems, limiting their application to smaller, more superficial vessels despite hemoglobin being these visible light sources main photoacceptor. Although lasers and light sources in the near infrared waveband can penetrate deeper into tissue, concomitant with longer wavelengths, the pigment in hemoglobin becomes less of a powerful photoacceptor, being replaced by proteinaceous and other molecular targets and, after around 900 nm, water. Diode-based laser systems have lately been reported in the treatment of leg veins because of their ease of generating true continuous pulses of longer duration compared with flashlamppumped systems such as the Nd:YAG and pulsed dye lasers in which the long pulsed versions consist of a train of micropulses due to the difficulty in obtaining a continuous long pulse from flashlamp pumping, thus offering greater efficacy with less in the way of side effects [1 5]. Radiofrequency (RF) current has recently attracted attention for lifting and tightening lax photoaged skin [,7]. Even more recently, a combination of optical energy and RF has been reported as an effective means of treating cutaneous conditions such as hair removal and for nonablative skin rejuvenation [8,9], and also in preliminary studies for leg veins [10,11]. Based on these data and the interesting combination of the energy/tissue interactions of phototherapy and RF therapy, the present study was undertaken to determine the safety and efficacy of a system combining these modalities using a proprietary electro-optical synergy (ELOS) technology, a new approach that combines 900 nm diode laser energy with bipolar RF current and applies them almost simultaneously to tissue for the treatment of different types of vascular lesions including leg veins, and to add further data from an extended patient population to the previous study on the same device [11]. *Correspondence to: Mario A. Trelles, MD, PhD, Instituto Médico Vilafortuny/Antoni de Gimbernat Foundation, Av. Vilafortuny 31, E CAMBRILS, (Tarragona), Spain. imv@laser-spain.com Accepted 31 October 005 Published online 9 February 00 in Wiley InterScience ( DOI /lsm.080 ß 00 Wiley-Liss, Inc.

2 18 TRELLES ET AL. SUBJECTS AND METHODS Subjects Forty eligible female patients were enrolled into the study, 7 58 years of age, (mean age years), with a variety of leg vein lesions. Although patients may have presented with leg veins in multiple sites, for this study only one site per patient was treated and followed up. Table 1 gives details of the patient characteristics. Exclusion criteria included pregnancy, photosensitivity, diabetes, and any history of bleeding, coagulopathies, or scarring. The study was approved by the Ethics Committee of the Antoni de Gimbernat Foundation. All patients, after TABLE 1. Patient Ages and Characteristics Related to Skin Phototype and Previous Treatment Patient Age Skin type Previous treatment 1 30 IV 31 IV 3 40 III Sclerotherapy 4 55 III 5 49 IV 53 II 7 5 IV Sclerotherapy 8 3 III 9 53 III II IV 1 34 III 13 4 III Sclerotherapy II II 1 3 II III IV II 0 53 IV 1 7 IV Sclerotherapy 3 II Sclerotherapy 3 3 III 4 37 II 5 9 III 3 III 7 4 III 8 3 III Sclerotherapy 9 55 IV III 31 8 II Sclerotherapy 3 35 IV 33 3 III III IV 3 II II II III III Sclerotherapy having been informed of the purpose and possible outcomes of the study, signed forms of consent for the study and clinical photography. All patients were examined before starting the study to confirm that the saphenous vein and its collaterals were competent without reticular or perforating vessels. The Duplex Ultrasound evaluation was performed with a ATL 1 Ultramark 1 9HDI TM (SomaTechnology, Inc., Chershire, CT). Eight patients of the 40 had received previous treatment (sclerotherapy). Skin phototypes varied from II to IV (1 type II, 17 type III, and 11 type IV). Vessels selected for treatment were blue or red in color, were located in the legs and ranged in diameter from 1 to 4 mm. Table gives details of the characteristics of the vessels and the number of treatments required. Patients were enrolled into the study on the understanding that they would have treatments at -week intervals up to a maximum of three treatment sessions. Treatment could be stopped, however, when the results were satisfactory for both the patient and the doctor in charge of treatment, or when the patient was satisfied with the outcome and the doctor agreed that further treatments might not obtain significant improvement. Patients were asked to come back for control of possible complications weeks after the last treatment and at - and -month assessment points after their last treatment session. Device and Parameters A Polaris LV (Syneron Medical Ltd., Yokneam, Israel) system was used in the study, incorporating the new ELOS technology that combines 900 nm diode laser energy with RF current and applies them virtually simultaneously to tissue for the treatment of different types of vascular entities. The pulse configuration of the dual modality device is square. The treatment head at the tip of the handpiece consists of a1cm quartz window, through which the laser energy is delivered, and which is sandwiched between the two electrodes which deliver the RF current to the target tissue. Epidermal cooling is effected by circulated cooled water which cools down both the quartz window and the electrodes to 58C. The treatment head contains sensors, which allow the user to monitor correct contact and also galvanic skin resistance (GSR), shown on the control panel LCD screen: when the resistance reaches the ideal low point, the system can be fired to achieve maximum effect. The LCD display also shows the selected dosages for the 900 nm laser and the RF current, in addition to monitoring the temperature of the skin coolant. Dosage with the 900 nm diode laser varied from patient to patient according to their skin phototype. The average fluence used was 0 J/cm with a long exposure time of 50 millisecond. A maximum RF energy of around 100 J/cm 3 was used for all treatments. For each shot, the laser is fired first with the RF being delivered towards the end of the 50 millisecond laser pulse. Typically, a sequence of pulses was applied along the entire vessel length. Neither compression nor topical or any other type of anesthetic was utilized. After applying a thin layer of transparent coupling gel (Aquasonic Clear

3 COMBINED DIODE LASER/RF FOR LEG VEINS 187 TABLE. Vein Characteristics and Number of Treatments for Each Patient # Vein caliber Color Location No. of treatment 1 x R A 3 x B C 3 x B T 3 4 x B T 5 x B C x R T 1 7 x B C 8 x B A 3 9 x R C 3 10 x B T 1 11 x R A 1 1 x R T 1 13 x B A 14 x B T 1 15 x B T 1 x R T 3 17 x B C 1 18 x B T 1 19 x R T 0 x B T 1 x R T x R T 3 3 x R T 4 x B T 5 x R T 1 x R A 7 x B C 1 8 x R A 1 9 x B T 1 30 x B C 31 x R C 3 3 x B T 33 x R C 34 x B C 3 35 x B T 3 x B A 1 37 x B T 38 x R A 3 39 x R T 40 x B C Vein Location: (T) Thigh, (C) Calf, (A) Ankle. Color: (R) Red, (B) Blue. Ultrasound Gel), the tip of the handpiece of the system was applied to the first treatment site with slight pressure to ensure good coupling of the RF electrodes with the target tissue and optimum cooling of the surface of the skin. The longitudinal axis through the electrodes of the treatment head was matched with the longitudinal axis of the vessel to be treated (Fig. 8). The treatment head was then moved forward (without firing) by the width of the electrodes to precool the next treatment area, then moved back to the first already cooled area and fired with the trigger incorporated in the handpiece, maintaining pressure on the trigger, and at the end of the treatment pulse (at a repetition rate of 1 Hz) the handpiece was then moved forwards to the second precooled treatment point where the system was fired again. While still maintaining pressure on the trigger, the operator moved the handpiece back to the previous point and the treatment was repeated, once again followed by the second target point, repeated as often as required until the desired endpoint (appearance of mild erythema, or visible collapse of the vessel) was attained. This process of treating each set of two points by moving the handpiece forwards then backwards (which we refer to as the forwards backwards technique) was repeated for subsequent sets of two target points until the end of the vein being treated was reached. Thus every treatment point received as many passes as required to achieve the endpoint, without any epidermal damage being noted due to the efficient pre- inter-, and post-treatment cooling technique. No compression was applied after treatments. Treatment Results Results were assessed after each treatment and at and after the final treatment session. Side-effects and resulting complications were recorded at each visit and at the -week, - and -month follow-ups. Patients were asked to grade the pain associated with the treatment on a visual analog scale of 0 100% at each treatment visit. From previous pilot studies on volunteer subjects (data not shown), the maximum threshold of pain delivered was established at 0% on the pain scale, while 50% or under was considered the ideal target. Uniformly colored self-adhesive paper seals as stable reference point markers were applied to frame the leg veins to be treated for the use of the computer program as will be explained later. Photographs were taken using digital camera macrophotography (Sony MAVICA MVC- FD91, MPxl, Tokyo, Japan), at a high resolution setting, before and after each treatment and at the - and -month follow-ups. Additional photography was taken whenever considered necessary to record results and treatment progression. Distance, angle, and light conditions were noted to ensure as similar a field as possible for all photographs. The digital photographic data for each patient were stored on separate floppy diskettes and kept in each patient s file. Biopsies of the treated and the untreated area (at certain distances from the treated spot, but of the same vessel), were taken pre- and immediately post-treatment from 10 patients as a cross sample for histological analysis. Staining techniques used were hematoxylin/eosin (H&E) and Masson trichromic stain. The desired macroscopic visual endpoints of treatment were vessel blanching, vessel darkening, or erythema above the vessel. Evaluation of Results Subjective patient assessment. Before and after each of the treatments and at and after the

4 188 TRELLES ET AL. final session, patients were asked to rate their satisfaction with the result on a five-item scale. Scale grades were Very Good, Good, Fair, Poor, and Worse and values were expressed as a percentage of the number of patients. The patient numbers from the Very Good and Good categories only were expressed as percentages of the total population and combined to give the patient satisfaction index (SI). Objective clinician assessment. Objectively, an independent vascular surgeon assessed the efficacy of the treatment from the clinical photography before and after each treatment and and after the last treatment session. Improvement was rated on a five-point scale as 75% 100% clearance, 50% 74% clearance, 5% 49% clearance, <4% clearance and exacerbation of the lesion compared with the pretreatment findings. These clearance rates corresponded to the five-item subjective patient assessment scale. The results from the 75% 100% and 50% 74% clearance were expressed as percentages and combined to give the overall improvement rates at the - and -month assessments, which were then compared with the patient SI values. Data Analysis by the Computer Program The digital pictures were all first normalized for hue, tint, color temperature, brightness, and contrast based on the colored seals. The silhouettes of the vessels were then outlined with computer-generated data based on a Canny operator-based edge-detection program (see the Appendix for details). This software was developed together with the Department of Computer Architecture, the University of Málaga (Spain) (MM-V, ORT). The before and the after pictures were analyzed and a clearance grade was assigned by the computer to each patient for the - and -month assessments. The clearance scale followed the same scoring system as the clinician s assessment scale. RESULTS All 40 patients completed the study. Nine patients required 3 sessions, 19 required, and 1 needed only 1 treatment. The initial reaction after treatment usually appeared as vasospasm, followed by erythema above the vessel lasting about 4 48 hours. Figure 1 illustrates typical results of the Polaris LV treatment (Patient #5), before (A) and immediately after treatment (B), and at the -month follow-up examination (C) after only one treatment. Figure A (Patient #9), shows several vessels of 4 mm in diameter located on the thigh immediately after treatment, and Figure B presents the situation at after the one treatment. The rate of complications was extremely low (Table 3). Most immediate side effects resolved completely within weeks. Other symptoms, such as hypochromia (one patient), lasted over 1 month but had mostly resolved at the time of the last assessment. Matting was visible weeks after the first treatment in five patients, remained visible in only two patients at the -month assessment and had almost completely resolved by the last assessment, after the last treatment. As for pain, 10 of the Fig. 1. Patient #5. A: mm vessels in the thigh. Notice the placing of the colored paper seals providing measurement references for the computer analysis, (B) immediately after treatment, (C) after one treatment, the vessel silhouette is significantly reduced. [Figure can be viewed in color online via

5 COMBINED DIODE LASER/RF FOR LEG VEINS 189 in any patient. Furthermore, there was no relationship between skin phototype and the degree of pain. Subjective Patient Assessment The patient self-assessment grades at and after the last treatment are illustrated in Table 4, from which it can be seen that at nine patients assessed their satisfaction with the result as Very Good (.5%); 17 as Good (4.5); 7 as Fair (17.5); and 7 as Poor (17.5). The -month patient SI (combined scores for Very Good plus Good ) was 5%. At the -month assessment, patients assessed their satisfaction with the result as Very Good (15%); 1 as Good (5.5%); 7 as Fair (17.5%); and as Poor (15%). The -month patient SI was 7.5%. There was no Worse result at either assessment point. Fig.. Patient #9. A: 4 mm vessels in the thigh, before treatment and (B) after only the one treatment. The vessels have practically disappeared. [Figure can be viewed in color online via 40 patients reported experiencing painful treatment (around 0% on the pain scale). For the 30 other patients, pain was graded under this threshold. No patient refused further treatment due to pain, and no anesthetic was used Objective Clinician Assessment The clinician assessment of vessel clearance based on the clinical photography at the and assessment points is also seen in Table 4. Fourteen patients (35%) achieved a clearance rate of from 75% tp 100% (very good); 14 (35%) from 50% to 74% (good); 10 (4%) from 5% to 49% (fair); and in the remaining (5%) the clearance rate was less than 4% (poor). At the -month assessment, the values for the same clearance rates were 50%, 3.5%, 10%, and 7.5%, respectively. The overall efficacy at and was 70% and 8.5%, respectively. In other words, at the -month assessment, 8.5% of the subjects achieved a clearance rate of over 50%. The values for the clinician assessment of the overall efficacy at both the - and -month assessments were higher than the patients SI scores for the same period, demonstrating as in previous reports that patient expectations may be slightly unrealistic, despite being prepared for this in the pretreatment patient orientation and education program. Computer Data Analysis The values for the computer-assessed vessel clearance (also in Table 4), based on the same clearance rates as in the clinician assessment at the - and -month assessments, were 35% and 47.5%; 37.5% and 35%; 5% and 15%; and.5% and.5%, respectively. The computer-assessed TABLE 3. Side Effects of Treatment Side effects and complications Immediately after last treatment weeks after last treatment after last treatment after last treatment Blisters Pain (over 0% on the scale) Bruising Erythema Crusting Matting 0 3 Hypochromia

6 190 TRELLES ET AL. overall efficacy at and was, therefore, 7.5% and 8.5%, respectively. The computer-generated data showed vessels decreasing in size, area, and number from the first treatment with favorable evolution at the final assessment after the last treatment. Figure 3 presents a typical example of the computer analysis of data generated by scoring the percentage changes in the vessels in the treated area, based on the edge-processing of the pretreatment and final assessment digital images. Figure 3 and Table 5 collate the data from Table 4, Figure 4 shows graphically a comparison between the patient, clinician, and computer assessments at the - and -month assessment points. The clinician and computer assessments were in general better than the patient assessments, with the exception of the good category. Table 5 further examines the relationship between the - month clinician assessments and both skin type and vein caliber. The darker skin types responded better, with 94% and 8% of patients with skin types III and IV achieving 50% or better clearance, compared with % of skin type II patents. Larger caliber veins responded better, with 88% of patients with veins greater than mm in diameter achieving 50% or better clearance, compared with 71% of smaller caliber veins. Histological Findings Results of histology in 10 patients before treatment showed normal epidermis with the presence of dilated vessels of typical varicose configuration. Immediately after treatment, the epidermis appeared normal whereas the dermal collagen presented with damage to the fibers specifically located around the target vessels (Fig. 5A,B). Histological differences before and after treatment could be clearly detected. Pretreatment, blood vessels were normal while in post-treatment samples, vessels appeared contracted and the hyalinization phenomenon of fibers was apparent together with perivascular edema due to heat damage, principally well-detected in the Mason trichromicstained tissue surrounding the target vessels (Fig. ). Fibers presented eosinophilic changes and vessels showed signs of sclerosis due to changes in their endothelium. Vessel walls demonstrated post-treatment contraction and had a twisted and anfractuous appearance, which changes were possibly a consequence of the combination of the different origins of heat damage associated with this dual modality approach as discussed below (Fig. 7A,B). DISCUSSION The system used for treatment was based on the synergistic combination of electro-optical energy, that is, diode laser energy and RF current, coupled with continuous and efficient epidermal cooling through the water-cooled treatment head kept in constant contact with the epidermis. A long pulse of a relatively low level of laser energy was immediately followed by treatment with a bipolar RF current conducted through the target tissue, the combination of which heated the target blood vessels to the appropriate temperatures. All patients in the study TABLE 4. Side-by-Side Comparison of the Subjective Patient SI Grades and the Objective Clinician and Computer Program Improvement Rates # Assessment at and Patients MD Computer 1 P P P P F F G G G VG G VG 3 G G G G VG VG 4 F G G VG F G 5 VG G VG VG VG VG VG VG VG VG VG VG 7 F F F G G G 8 F F F G G G 9 F F F G G G 10 P P P F P F 11 VG G G VG G VG 1 G VG VG VG G VG 13 G G VG VG VG VG 14 P P F F F F 15 G G G G G G 1 G G VG VG G VG 17 P P F F F F 18 VG G VG VG VG VG 19 P P F P F F 0 G G G G G G 1 P P F F F F F F F G G G 3 VG VG VG VG VG VG 4 VG G VG VG VG VG 5 G G VG VG VG VG G G G VG G VG 7 G VG VG VG VG VG 8 G G G G VG VG 9 VG VG VG VG F G 30 G G G VG G VG 31 P P F G G G 3 VG G G G VG G 33 G G G G G G 34 F G G VG G VG 35 G G G G F G 3 G F G G F G 37 G VG VG VG VG VG 38 F F F P F P 39 G G VG VG VG VG 40 VG G VG VG VG VG Assessment: For patients, (VG) Very Good, (G) Good, (F) Fair, (P) Poor (there were no worse assessments); For clinician and computer, VG ¼ 75% 100% vessel clearance, G ¼ 50% 74%, F ¼ 5% 49%, P ¼ <4%.

7 COMBINED DIODE LASER/RF FOR LEG VEINS 191 Fig. 3. Patient #4. Upper row (A) vessels in the thigh before and at the - and month- assessments. Two treatments were given. Second row: (B), selection of treated area for analysis in relation to pre-treatment findings, and at the - and month assessments, (C) the computer programme defines the vein silhouette via pixel analysis, (D), signal noise, generated by pigmented disorders and pores, for example, is eliminated. The veins are extracted from the whole image, and this signal is calculated as a percentage with respect to the selected area of analysis, (E) the computer-calculated reduction rates obtained by the treatment are given in the inset table. [Figure can be viewed in color online via were treated with an average laser energy of 0 J/cm, and 100 J/cm 3 of RF, which resulted in high clearance scores for both large and small vessels. Average clearance for small vessels (< mm) was less than for large vessels ( > mm), and darker skin types tended to respond better than lighter (Table 5). However, even in the lighter type II skin, % of subjects achieved clearance better than 50%. Side effects were minimal. Taken together, these data suggest that the combined 900 nm diode laser and RF system was effective and safe for TABLE 5. Results at the and Month Assessment Points After the Final Treatment Comparing the Evaluations by Patient, Doctor, and Computer (From Data in Table 4). The Clinician -Month Assessment Results Are Further Correlated With Patient Skin Type and Vein Caliber Results Patient Doctor Computer Skin type (% of patients) Vein caliber II (n ¼ 1) III (n ¼ 17) IV (n ¼ 11) < mm Very (33) 11 (5) 5(45) 7 13 Good Good (33) 5 (9) 4 (37) 3 10 Fair (17) 1 (3) 1 (9) Poor (17) 0 1 (9) 1 Worse > mm

8 19 TRELLES ET AL. Fig. 4. Patient, clinician and computer - and -month assessments compared by grade. No patient was graded worse. For the clinician and computer grading, very good, good, fair, and poor correspond to vessel clearance rates of 75% 100%, 50% 74%, 5% 49%, and <4%, respectively (based on data from Table 4). [Figure can be viewed in color online via leg vein treatment at the parameters used in the present study. The fluence (0 J/cm ) is very low when compared to the fluences usually used with laser diode to treat leg vein telangiectases and emphasizes the role of RF energy. For example, Kaudewitz et al. [1] used J/cm with a 940 nm diode laser and Levy et al. [13] used energy densities of J/cm (980 nm laser diode) to achieve a 50% clearance on 0% of patients. Passeron et al. [14] used J/cm 3 (940 nm laser diode) to obtain efficient vessel clearance on mm leg veins. So, the observed rate of success is comparable to, if not better than, results obtained in these studies. They are also very similar to other studies using Nd:YAG laser long- pulse technology. Weiss [15] and Sadick [1] have reported, respectively 75% and 8% of vessel clearing. Moreover, when using Nd:YAG or diode lasers alone, even using a very aggressive cooling, pain was relatively high for a majority of patients The use of comparatively low levels of laser fluence (0 J/ cm over 50 milliseconds gives an incident irradiance of only 40 W/cm ) coupled with the forwards backwards pre-, inter- and post-pulse cooling helped to minimize damage to the epidermis which is a major risk associated with laser- and light-based devices, and when the laser/ tissue interaction at 900 nm is taken into consideration, namely absorption in the molecular components of biological pigments and tissue proteins, and to a lesser extent, water, energy at this wavelength is capable of comparatively deep penetration into target tissue, thus allowing targeting of deeper dermal vessels (Fig. 8) [17,18]. An RF current works by creating heat in the target tissue depending on the impedance of the tissue, that is, the total opposition (resistance, capacitance, and inductance) offered to the flow of an alternating current: the higher the impedance for a given current and frequency, the greater the degree of the electrothermal reaction. Fig. 5. Skin 50, H&E. A: Untreated skin shows a normal epidermal pattern. A large, dilated vessel can be observed in the dermis. B: In the dermis, immediately after treatment, the vessel is closed with formation of perivascular edema and coagulation of the dermal collagen fibers. Heat causes coagulation and the inflamed dermis around the vessel compresses the endothelium producing vasospasm. [Figure can be viewed in color online via Conversely, tissue of lower impedance offers less resistance to the current, less heat is generated, and in the presence of such an impedance gradient electrical current will seek out the path of least resistance. The device in the present study used bipolar conductors. Based on the distance between these conductors, a reasonably accurate calculation of the depth of penetration of the high-frequency current can be made (one-half of the inter-electrode distance) as it is conducted through the target tissue from one conductor to the other [19]. In the case of the system in the current study,

9 COMBINED DIODE LASER/RF FOR LEG VEINS 193 Fig.. Skin 50, Masson trichromic. Immediately after treatment, the epidermis appears normal and uninjured. A completely coagulated and occluded blood vessel can be seen in the dermis. There is clear damage to the collagen fibers with evidence of the hyalinization phenomenon, specially around the damaged vessel. [Figure can be viewed in color online via the distance is mm, thereby giving penetration to at least 3 mm. The authors hypothesis for the combined action of the diode laser and RF energy is as follows. The 50 millisecond pulse of 900 nm laser energy heats up the vessel and the tissue round it from the inside out, while the epidermis is protected through the efficient contact cooling. The RF current is delivered at the end of the 50 millisecond pulse, and through the skin resistance develops more heat in the already heated area, travelling from the outside of the Fig. 7. Skin 50, Masson trichromic. A: Before treatment: Normal epidermis and in the dermis, a dilated varicose vessel in noticed with blood in its interior. B: Immediately after treatment, the vein has collapsed and appears twisted and wrinkled with its lumen closed. Damage and sclerosis can be seen in the vein endothelium. [Figure can be viewed in color online via Fig. 8. Relative penetration of light across the visible and IR spectrum into human skin in vivo, based on a transmission photospectrogram of the human hand adapted from references 1 and 13. Visible light in the blue/green and green wavebands is absorbed in biological pigments, thus preventing deep penetration. Red light is less absorbed in these pigments, particularly hemoglobin, and so penetrates deeper. However, the deepest penetration is obtained in the near IR waveband up to around 900 nm due to the window at nm in the water absorption curve and less pigment specificity per se, after which the increase in water absorption begins to play a role. vessel inwards in a centripetal manner. We believe it is this combination of the centrifugal and centripetal heating effects which is responsible for the good vein closure illustrated in the histology, where the vessels were not only closed but also tortuously folded and twisted but without fracture of the endothelium (the anfractuous phenomenon ) [14] as illustrated in Figure 7. The fact that a sequence of combined laser and RF pulses was used over the target vein in our forwards backwards technique possibly further improved the effective photoand electrocoagulation of the target veins. Mordon [0] has reported enhanced photocoagulation of veins when a series of laser pulses were used for leg vein treatment. He proposed that the process of methemoglobin formation, initiated with the first pulse, changed the optical condition of blood and thus its absorption characteristics, making the photothermal action of the following pulses more effective. In a series of pilot studies with the system to identify the ideal parameters, the -week treatment regimen was found to be most efficient at ensuring consistently good closure of the target vessels in patients where more than one treatment session was required, and could be applied at this interval because the epidermis had been well-protected from damage during the previous treatment by the very efficient epidermal cooling. The longer inter-treatment interval more commonly reported in the literature, from 1 to

10 194 TRELLES ET AL., presents the possibility of some recanalization of the treated vessel so that treatment would have to start again almost from the beginning. We believe the -week interval probably allowed reinforcement of the previous treatment while the vessel was still recovering and the vessel walls were still coated, thus ensuring complete and lasting closure. Another point for consideration is that, during the treatment, a package of heat damage was delivered to the entire target vessel and, to a lesser extent, its overlying and surrounding tissue. In the remodeling phase of the subsequent wound healing process, a layer of mildly fibrotic tissue, more optically dense than the normal dermal tissue, could be expected to form over the treated vessel and thus help improve the final treatment result by inserting a biological filter of higher optical density between incident light and the treated vessel, thereby helping to conceal the latter. This mechanism could possibly explain the better results seen by both clinician and computer at the -month compared with the -month assessment. The main obstacle to evaluating treatment results is the variation in the appearance of vascular lesions depending on vessel size, depth, and density of skin pigmentation. In the present study, in addition to the objective clinical assessment, the vessel clearance rate was calculated by Canny processor-based image processing of digital pictures taken before and after treatment. Average clearance was calculated as the difference between the area of the lesion before and after treatment. Stable reference point markers (adhesive paper seals of the same color) placed to delineate the area of interest provided a constant color reference from which the computer could produce a perfectly colormatched image despite any minor differences in color temperature at each session [1]. The combination of the clinical photography and the computer data generated from it (see the Appendix for details) may well help to minimize the disparity between the subjective and objective clinician-rated improvement rates seen in this study in the very good scores at the -month assessment (.5% at down to 15% at, Table 5, Fig. 4). Very often patients will not remember just how they were before treatment, especially over a -month assessment period. So these computergenerated data provided a completely objective index for the vein clearance rate, and should prove very useful, in combination with the clinical photography, in allowing patients to appreciate the real improvement which they themselves might not see, and which could be expected to improve even more with time as remodeling progresses []. ACKNOWLEDGMENTS The authors thank Syneron Medical Ltd. for providing the data needed to complete part of this manuscript. The clinical and laboratory subject matter of this paper is registered in the medical investigation activities of the FUNDACION ANTONI DE GIMBERNAT (year 004/5). Appendix The Computer assisted system for the objective assessment of Vein elimination A generic, modular, and expandable edge-detection based computer platform was applied in this study which was first presented in 003 [] allowing userfriendly image manipulation, sample extraction, and assisted evaluation of tissue features. The software platform is designed to evaluate image-tissue indices and to identify individual or combined descriptors, which will more accurately represent differences in venous outlines. These differences represent an objective measurement that would assist greatly in diagnosis and means of treatment, and subsequently allow objective assessment of the improvement at various stages of treatment. The system also enables the tracing and linking of samples with the original source of data, so at any time, it is possible to maintain the relationship between the samples and even connect the system to the clinician s clinical records database to enable real-time data recording. For the present study, in all cases, patients were photographed at the same distance using digital macrophotography (Sony Mavica MVC-FD91, MPxl, high resolution setting). Ambient conditions and illumination were specially controlled. The recorded image corresponded to a whole treated area from which image samples were extracted. Samples were automatically normalized, removing noise, standardizing the brightness, scaling (i.e., adjusting the distance between external markers), and adjusting contrast and luminosity parameters. All these procedures were performed by the computer program. An automatic edge detector procedure was used to closely identify the faint and ruffled margins of the target veins. This Canny process is combined with a growing region algorithm able to detect the area of the veins. A thresholding procedure has also been implemented to remove noise. In this way, the pre- and post-treatment areas of the affected zone in each image are computed. These values can be used as a sensitive and objective comparative measurement not only for diagnostic reports on the pre-treatment condition of veins, but also for demonstrating the improvement and efficacy of the prescribed treatment. More information on the platform for those interested can be found on the platform web site at: htm REFERENCES 1. Passeron T, Olivier V, Duteil L, Desruelles F, Fontas E, Ortonne JP. The new 940-nanometer diode laser: An effective treatment for leg venulectasia. J Am Acad Dermatol 003; 48: Trelles MA, Allones I, Trelles O. An 810 nm diode laser in the treatment of small (10 mm) leg veins: A preliminary assessment. Lasers Med Sci 004;19:1. 3. Varma S, Lannigan SW. Laser therapy of telangiectatic leg veins: Clinical evaluation of the 810 nm diode laser. Clin Exp Dermatol 000;5: Kaudewitz P, Klövekorn W, Rother W. Effective treatment of leg vein telangiectasia with a new 940 nm diode laser. Dermato Surg 001;7:

11 COMBINED DIODE LASER/RF FOR LEG VEINS Passeron T, Olivier V, Duteil L, Desruelles F, Fontas E, Ortonne JP. The new 940-nanometer diode laser: An effective treatment for leg venulectasia. J Am Acad Dermatol 003;48(5): Jacobsen LG, Geronemus RG. Treatment of nasolabial folds and jowls with an non invasive radiofrequency device. Arch Dermatol 003;139: Fitzpatrick RE, Geronemus RG, Goldberg DJ, et al. Multicenter study of noninvasive radiofrequency for periorbital tissue tightening. Lasers Surg Med 003;33: Sadick NS, Makino Y. Selective electro-thermolysis in aesthetic medicine: A review. Lasers Surg Med 004;34: Laughlin SA. Depilación efectiva de pelo blanco utilizando la combinación de radio-frecuencia y energía óptica. Salud Estética 003; Chess C. Prospective study on combination diode laser and radiofrequency energies (ELOS) for the treatment of leg veins. J Cosmet Laser Ther 004;: Sadick NS, Trelles MA. A clinical, histological, and computerbased assessment of the Polaris LV, combination diode, and radiofrequency system, for leg vein treatment. Lasers Surg Med 005;3: Kaudewitz P, Klovekorn W, Rother W. Treatment of leg vein telangiectases: 1-year results with a new 940 nm diode laser. Dermatol Surg 00;8(11): Levy JL, Berwald C. Treatment of vascular abnormalities with a long-pulse diode at 980 nm. J Cosmet Laser Ther 004;(4): Passeron T, Olivier V, Duteil L, Desruelles F, Fontas E, Ortonne JP. The new 940-nanometer diode laser: An effective treatment for leg venulectasia. J Am Acad Dermatol 003;48(5): Weiss RA, Weiss MA. Early clinical results with a multiple synchronized pulse 14 nm laser for leg telangiectasias and reticular veins. Dermatol Surg 1999;5: Sadick NS. Long-term results with a multiple synchronizedpulse 104 nm Nd:YAG laser for the treatment of leg venulectasias and reticular veins. Dermatol Surg 001;7: Smith KC. The science of photobiology. NY, NY; Plenum Press; p Smith KC. The photobiological basis of low level laser radiation therapy. Laser Ther; 1991;3: Trelles MA. The combination of optical and electrical energies produces different histological findings from when laser alone is used in leg vein treatment. Lasers Med Sci 004;19: Mordon S, Brisot D, Fournier N. Using a non uniform pulse sequence can improve selective coagulation with a Nd:YAG laser (1.0 mm) thanks to met-hemoglobin absorption: A clinical study on blue leg veins. Lasers Surg Med 003;3: Trelles MA, Martín-Vázquez MJ, Trelles O. Objective followup by computational evaluation of tissue changes alter light treatment. Lasers Med Sci 003;Vol. 18. Supplement 1.. Trelles MA, Allones I, Martín-Vázquez MJ, Trelles O, Vélez M, Mordon S. Long pulse Nd:YAG laser for treatment of leg veins in 40 patients with assessments at and 1. Lasers Surg Med 004;35:8 7.