Laser Venous Interventions
From the Academic Vascular Surgical Unit, Hull Royal Infirmary, E. Yorks, United Kingdom.
Disclosure: Dr. Carradice and Dr. Chetter disclose that Diomed (Cambridge, U.K.) provided research grants (50% of a research nurse’s salary over a 12-month period) to facilitate trials at Hull Royal Infirmary, but had no involvement or influence in the drafting, or decision to publish this or any other paper.
Manuscript submitted September 12, 2008, provisional acceptance given December 2, 2008, accepted December 11, 2008.
Address for correspondence: Daniel Carradice, MD, Academic Vascular Surgical Unit, Hull Royal Infirmary, Anlaby Rd, Hull, E Yorks HU3 2JZ, United Kingdom. E-mail: [email protected]
Varicose veins are a common problem, affecting 10–23% of men and 30–40% of women, and are known to impair health-related quality of life. Surgery is the most commonly employed treatment in the U.K. It has been shown to improve quality of life overall and is highly cost effective. Negative aspects include quality of life impairment in the immediate post-operative period and disappointingly high long-term recurrence rates.
Three new minimally invasive treatments have emerged to try to address these shortcomings: foam sclerotherapy, radiofrequency ablation (RFA) and endovenous laser treatment (EVLT).
This review describes the principles of these treatments, with particular emphasis on EVLT. Current best evidence is presented and discussed with specific references to key outcomes of anatomical success, safety, quality of life and economic impact.
Evidence suggests that EVLT is the most efficacious procedure currently available for the treatment of varicose veins in the short and medium term. This is based upon enhanced anatomical success, 95.4% at 5 years (cf. surgery, 75.75%, RFA, 79.9% and foam, 73.5%), and improved quality of life up to 3 months, featuring reduced pain, an earlier return to function and few significant complications.
Further evidence is required and large randomized clinical trials (RCTs), centered on quality of life and offering economic analysis, are eagerly awaited.
Varicose veins (VVs) are a common problem, with a prevalence of 10–23% in men and 30–40% in women.1 VVs are not solely a cosmetic concern, but impair health-related quality of life (QoL).2–4 Most patients suffer symptoms (aches, discomfort, pruritis and muscle cramps) and a proportion will develop complications, including edema, eczema, lipodermatosclerosis, ulceration, phlebitis and bleeding.
Surgery is the most commonly employed treatment in the United Kingdom.5 The REACTIV trial6 clearly demonstrated that surgical treatment results in significant improvements in QoL and is cost effective (incremental cost-effectiveness ratio of £1,936 (USD 2,845) per quality-adjusted life-year over 10 years). VVs therefore can and should be treated (Table 1).
Surgery is not ideal. It results in a temporary deterioration in postoperative QoL (as seen with most invasive treatments).4,7 This is likely due to the local morbidity associated with groin dissection and the trauma of vein stripping. Surgery leads to painful and prolonged recovery in some patients, and poses the risks of infection, hematoma and nerve injury.8,9
Recurrence following surgery is significant, with persistent reflux in up to 30% of cases at 1 year, 40% at 2 years and up to 60% beyond 10 years on duplex scanning.10–14 Many centers, however, find that their figures are lower and one must be cautious when interpreting duplex outcomes, as symptomatic recurrence is much lower. Despite this, approximately 20% of procedures are performed for recurrent VVs.15,16
The decline in QoL, complications and recurrence of symptoms, perhaps coupled with an element of unrealistic expectations, results in dissatisfaction with surgical treatment in up to a quarter of National Health Service (NHS) patients.17
A range of minimally invasive treatments have been developed, which are planned and performed under ultrasound guidance.
Liquid sclerotherapy has been performed for many years. It uses a chemical irritant injected into the vein, initiating inflammation in the vein wall. The results of liquid sclerotherapy were disappointing and led to a decline in its use; however, the mixture of the sclerosant (polidocanol or sodium tetradecyl sulphate) with air or carbon dioxide to produce a foam injected into the vein under ultrasound guidance seems to yield much better results. Foam sclerotherapy is now used to treat both truncal and segmental VVs.
Radiofrequency ablation (RFA) utilizes thermal energy to occlude the vein. An electrode is inserted into the vein and passes an electrical current through the wall, directly heating it to around 80˚C. Another similar device (VNUS ClosureFAST, San Jose, California) uses indirect thermal energy via the introduction of a heated coil into the vein. The temperature of the coil is automatically regulated to 120˚C. A problem with RFA techniques is that prior to the vessel wall, the blood is also heated, causing thrombosis. This thrombus insulates the wall from the heating effect and if insufficient energy is transmitted to the vessel wall, a thrombotic occlusion of the vessel, rather than destruction of the vein wall, results. The thrombus may later recanalize, causing recurrence.
Finally, endovenous laser therapy (EVLT) was developed and has since become the frontrunner of the new modalities.18
Principles of EVLT
EVLT utilizes the delivery of laser energy into the vein via an optical fiber. LASER (light amplification by the stimulated emission of radiation) produces a collimated (low divergent) “beam” of photons whose waves are coherent (in-phase), allowing a very intense and accurate delivery of energy, which can be monochromic (the same “color” or wavelength) (Figure 1). Commonly utilized wavelengths range from 810 nm to 1,320 nm. Shorter wavelengths are absorbed primarily by the hemoglobin in erythrocytes, whereas longer wavelengths are absorbed by intra- and extracellular water. Rapid heating of the blood (700–1,300˚C) creates steam;19 this, along with direct heating of the vein wall, causes collagen contraction and denudation of endothelium. The result is a nonthrombotic occlusion due to vein-wall thickening, luminal contraction and fibrosis of the vein. Three months following laser treatment, the vein becomes difficult or impossible to visualize on ultrasound.
EVLT is used to ablate all incompetent axial/truncal veins, most commonly, the long saphenous and short saphenous veins, but has also been used to treat perforators and the anterior saphenous and Giacomini veins. Segmental veins can then either be treated surgically, by sclerotherapy or simply left to regress.
There are several areas where procedural technique may vary between surgeons. Following is a description of the technique utilized at our center.
Thorough duplex evaluation is performed, allowing for accurate planning of the most appropriate procedure. All procedures are performed under local tumescent anesthesia in a dedicated procedure room within the outpatient department. Incompetent axial veins and perforators are preoperatively marked using duplex ultrasound and surface varicosities, also marked with the patient standing. Skin preparation and draping are performed prior to percutaneous cannulation of the axial vein, with the patient in the reverse Trendelenburg position. Ultrasound-guided cannulation is performed at the lowest point of demonstrable reflux. A 5 Fr catheter is introduced into the vein using the Seldinger technique. The tip is accurately positioned at the junction between the superficial and deep venous systems using ultrasound. The patient is then placed in the Trendelenburg position, and perivenous local anesthetic (20 ml of 2% lidocaine with 1:200,000 adrenaline and 20 ml bupivicaine in 1 L of 0.9% saline) is infiltrated along the vein and varicosities. A bare-tipped 600 nm laser fiber is introduced via the catheter. Laser energy is then delivered continuously using an 810 nm diode laser generator at 14 W power. The target linear energy delivery is 80–100 J/cm. One-centimeter incisions are made, allowing ligation of perforators, and ambulatory phlebectomy is performed through stab incisions. An elastic adhesive bandage is then applied to the leg, which is replaced with a Class II (30–40 mmHg) full-length graduated support stocking after 1 week for an additional 5 weeks. All patients are given regular non-steroidal anti-inflammatory drugs (NSAIDs) in the absence of contraindication or intolerance.
Outcomes of varicose vein treatment
The aim of developing any new technology is to improve on existing treatment. The aim of endovenous treatments is therefore to reduce or eliminate the deterioration in quality of life in the early post-surgical period, while retaining the same or improved clinical efficacy. Complication rates should also be as low, and preferably lower, than with surgery, and the cost effectiveness of treatment established.
The primary outcome for many studies is the duplex appearance of the treated veins, and most surgeons aim for complete ablation.
Two meta-analyses have been performed. The first20 found an occlusion rate of 95.9% (10,812/11,277) at the end of follow up for EVLT. For RFA, the rate was 81.9% (258/315), and for foam, 86.2% (904/1,049). The recanalization, recurrence or neorevascularization rate was 4.5% after EVLT. The second meta-analysis21 demonstrated a success rate (95% confidence interval [CI]) of:
• 92.9% (90.2–94.8) at 3 months;
• 93.3% (91.1–95%) at a year;
• 94.5% (87.2–97.7) at 3 years;
• 95.4% (79.7–99.1) at 5 years after EVLT.
This compared to:
• 80.4% at 3 months to 75.7% at 5 years for surgery;
• 82.1% at 3 months to 73.5% at 5 years for foam;
• 88.8% at 3 months to 79.9% at 5 years for RFA.
EVLT was therefore significantly better than surgery (p
Interestingly, the success rate of surgery significantly declined over time (p = 0.004), but this was not true for endovascular treatments. In the current era, the most common cause of recurrence following surgery is neorevascularization.10,11 It has been suggested that leaving patent competent groin tributaries intact, as with endovascular techniques, will preserve the normal physiological flow. Along with a lack of surgical dissection, this may reduce the angiogenic stimulation for neovascularization, decreasing late recurrence rates.
Recanalization post EVLT does not necessarily result in reflux. In one study of 30 patients with recanalization at 6–12 weeks, only 3 had reflux and were successfully ablated with a second treatment. Twenty-four were followed up to 1 year, and all showed significant improvement in their symptoms. Eight developed some evidence of low-volume reflux at 1 year.22
Quality of life
The main aim in the management of VVs is to alleviate symptoms and improve QoL, thus QoL outcomes are the most significant.
QoL may be analyzed using generic, disease-specific or domain-specific instruments. Commonly utilized generic QoL instruments include the Short Form-36 (SF36) and Euroquol (EQ 5D), which have been demonstrated to be valid and reliable.23–27 Disease-specific instruments, such as the Aberdeen Varicose Vein Questionnaire (AVVQ), assess the specific venous symptoms and their impact on QoL. The AVVQ has undergone rigorous assessment of validity and reliability.28,29 Domain-specific analysis, for example, of pain, may be quantified subjectively using visual analog scores. In addition, several other important outcomes, e.g., return to normal function or return to work, should also be assessed, but are frequently multifactorial.
The REACTIV trial6 established the QoL benefits of successfully treating VV with surgery. Unfortunately, there is a paucity of this type of data following endovascular treatments.
A meta-analysis20 identified two reports addressing QoL outcomes following EVLT. The first was a non-randomized pilot study30 and the second a RCT.31 EVLT results in significantly less pain (SF36 – Bodily Pain domain) than surgery up to 3 months (p
A since-published RCT32 failed to demonstrate any benefit in AVVQ scores, but did show that EVLT patients were returning earlier to normal activity than after surgery (p = 0.001). Failure to demonstrate QoL improvement may have been secondary to Type II error and also a failure to capture early post-procedural data (Mekako et al demonstrated QoL benefits at 1 and 6 weeks30).
With regard to RFA, earlier return-to-work times have been seen as compared with surgery (p = 0.00001; n = 171), but no difference in pain was observed (p = 0.28; n = 180).20
There have not been any differences shown between foam and surgery on any QoL outcomes.33
EVLT appears to be a very safe procedure and significant complications are rare. The most common side effect of treatment is bruising, which may be as high as 52.2%, but the extent of bruising has been shown to be less than after surgery (p = 0.003; n = 173).20 This increased bruising (compared with 9.1% for RFA) demonstrates the efficacy of EVLT, as the thermal energy acts upon the full thickness of the vein wall, ensuring closure. In fact, bruising has been linked to successful technique and is usually absent in treatment failures.34
Pigmentation has also been described, but this is often around phlebectomy sites and may be due to the underlying disease. We have seen pigmentation in 2.5% (5/198) of cases (compared with 21% with foam20). Superficial phlebitis may also happen (2.8%, 61/2,197), but it is less common than with RFA (3.2%).
Paresthesia is much less common with EVLT (1.7%, 168/10,085) than with RFA (10.99%, 341/3,102), but is still more common than with foam (0.004%, 3/8,464). Rates are lower than with surgery, but this failed to be significant (p = 0.32).20 DVT rates are low (0.3%, 27/9,317) after EVLT.20
Surgery is highly cost effective and its cost/QALY much lower than the commissioning threshold for the NHS.6
There has yet to be a thorough economic analysis of EVLT. One study found little difference between the basic cost of the EVLT and surgical procedures, although all procedures were performed under local anesthetic and no in-depth cost analysis was performed.31 Within our unit, all surgical procedures are performed under a general anesthetic, and EVLT is performed under local anesthetic in a procedure room. Excluding the capital costs of the laser generator and maintenance, the only extra outlay for EVLT is the procedural kit (£250/368USD). Surgery has the added costs of a general anesthetic (including pre-assessment) and occasionally also an overnight stay.
Thorough economic analysis is dependant upon robust QoL data concerning EVLT efficacy, allowing a cost-utility analysis. Early indications are that EVLT will have a similar or lower procedural expense than surgery, and with a more favorable QoL profile, it may prove to be more cost effective than surgery.
EVLT – Technique Refinement
Energy dose (ED)
The amount of energy delivered to a vein can be represented as linear energy density (ED) (J/cm) and a wide range has been used, from around 20–140 J/cm. Early techniques used 20–40 J/cm, but the magnitude of ED has been shown to be critical in the success of vessel closure. It was the single most significant predictor of success (p = 0.001) in one study, which demonstrated 100% occlusion at 3 months with an ED > 60 J/cm (810 nm laser) (irrespective of vessel diameter).35 Timperman found his successful closures had received 63.4 J/cm and his failures 46.6 J/cm (p 80 J/cm, he had 100% success.36 A second study using 95 J/cm, however, had only a 95% success rate.37
Other work has suggested that vein diameter is important and operators should aim for specific fluence based on estimated cross-sectional area (J/cm2).38 A problem with this approach is that vein spasm and tumescent anesthetic pressure cause the vein to approximate to the catheter. In addition, veins are not uniform in diameter, leading to imprecision and the need for complicated variable withdrawal rates. The use of fluence calculations has not yet had a vast effect on EVLT’s already excellent technical success rate. Thus far, no one has demonstrated an increase in complication rates by increasing the ED, as the perivenous local anesthetic acts as a heat sink.
Our unit aims to deliver 80–100 J/cm, which has not resulted in an increase in complications when compared to cases where lower EDs were utilized.
Wavelength and power
A spectrum of laser wavelengths are available for EVLT, which can deliver energy with a wide range of power in either a pulsed or continuous fashion.
The vast majority of EVLTs have been performed with 810 nm lasers,34 but 940 nm,19 980 nm39 and 1,320 nm40 have all been shown to have good duplex outcomes. Data comparing different wavelengths are scarce. An early study using longer wavelengths (1,064 nm) described skin burns in 5% (12/244) and a paresthesia rate of 38% (92/244).41 This was thought to be due to greater tissue penetration at longer wavelengths. These complications have not been seen with the 1,320 nm laser, and longer wavelengths may be associated with less pain.42,43 The largest study found that 33 patients treated with a 1,320 nm laser had less bruising (with 60% of the group having visible ecchymosis vs. 80%) and pain (with 50% complaining of any post-procedural pain vs. 75%) when compared with a 940 nm laser.42 Mathematical modeling suggests that lower energy delivery is required at longer wavelengths in order to induce full-thickness venous damage,44 though this is yet to be proven clinically.
Power settings are usually set to allow a reasonable withdrawal rate of the laser fiber and are typically between 10–15 W. The lower the power setting, the longer it takes to deliver the desired energy dose. Continuous delivery of laser energy allows uniform treatment of the vein length and typically results in shorter withdrawal times than pulsed delivery. No study has demonstrated any differences in efficacy or complications using pulsed versus continuous or different power settings, as long as ED and wavelength are kept constant.32,42
There is a lack of consensus on other areas of technique. Some surgeons perform EVLT on the axial veins, leaving branch varicosities to regress, but this leads to high numbers of secondary procedures and has been shown in an RCT to result in poorer QoL outcomes.45 Our unit performs concomitant phlebectomy and ligation of perforators, demonstrating enhanced improvement in QoL (at 6 weeks (p
Some surgeons position the fiber tip 2 cm away from the deep vein junction, on the principle that this will reduce the risk of DVT from propagation of thrombus from the treated vein. Some surgeons also routinely use anticoagulants for thromboprophylaxis. There is no evidence for either and the risk of DVT is very low. An intact, incompetent junction probably has the capacity to result in recurrence. Our unit aims for a flush occlusion and we do not use anticoagulant thromboprophylaxis, only pressure dressings and mobilization. We have not seen a single case of DVT, but detected 1 thrombus protruding into the femoral vein. This was treated with anticoagulation (therapeutic subcutaneous low-molecular-weight heparin) and resolved without sequelae at 6 weeks.
EVLT is known to be a safe treatment for varicose veins. It exceeds traditional surgery and all other treatments in terms of anatomical success. Early QoL data also suggest superiority over surgery up to 1 year.
Data regarding energy dosing and wavelength are lacking. However, exceeding an ED of 60 J/cm seems necessary to reduce failure rates. The vast majority of the excellent results of EVLT have been achieved using the 810 nm laser. Small studies have only demonstrated minimal benefits of longer wavelengths; thus, this issue remains debatable. In addition, it is probable that each wavelength will have its own optimal ED, varying with the relative differences of penetration in vivo.
The most important evidence is yet to be published: large randomized, controlled trials and series specifically analyzing key QoL outcomes. These data can then form the basis of a thorough economic analysis. These trials are currently underway.
• Varicose veins are a common problem.
• Successful surgical treatment results in significant improvements in health-related quality of life over time and is cost effective.
• There is a temporary decline in quality of life post surgery as well as disappointing recurrence rates.
• EVLT is a safe, local anesthetic procedure, resulting in few side effects and complications, and allowing immediate mobilization.
• EVLT offers significantly better anatomical results than surgery, radiofrequency ablation and foam sclerotherapy, resulting in lower recurrence rates up to 5 years.
• There is some evidence that EVLT results in improved quality of life in the first 3 months compared with surgery, as well as a faster return to normal life.