Introduction

Perforating veins (venae perforantes, perforator veins – PVs), pass through the fascia and connect the deep and superficial venous systems in the lower limbs.

Approximately 100 PVs are present in each lower limb [1]. Two thigh perforating veins are still commonly referred to by the eponyms of their discoverers, Hunter’s perforating vein and Dodd’s perforating vein. Four similar eponyms are used in the calf: one is named after Boyd, while the three most important in pathophysiological terms are named after Cockett. These perforating veins connect with the posterior tibial vein and drain into the saphenous vein. Cockett perforators play a major role in the development of a serious complication of chronic venous insufficiency, presenting as an ulcer on the medial aspect of the distal third of the lower leg (in the so-called “gaiter area”) (ulcus cruris, crux aegroti, crux medicorum) [2]. The relationship between IPV and chronic venous insufficiency was established in 1956–1960 by Dodd and Cockett [3].

According to the American Venous Forum 2023, an IPV is one revealing reflux lasting longer than 0.5 seconds on Doppler ultrasound (DUS). However, the European Society for Vascular Surgery guidelines state that “the definition of PV incompetence remains controversial. Perforating vein incompetence is characterised by having a net outward flow of > 0.35 seconds (or > 0.5 seconds, according to others) on DUS and a vessel diameter > 3.5 mm
is usually considered “pathological”, in particular in an area with skin changes.” [4, 5].

Perforating veins can demonstrate bidirectional flow. A dilated but competent PV may cause re-entry into varicose veins. Incompetent perforating veins are the most common cause of recurrent varicose veins after surgical treatment and may contribute to the progression of chronic venous insufficiency [6].

Incompetent PVs may act as a primary source of reflux or develop as a consequence of deteriorating global venous function and deep venous insufficiency [5].

Tolu and Durmaz [7] examined 2,000 lower limbs with DUS in patients with symptoms of venous insufficiency. Incompetent perforating veins were found in 27.5% of patients and varicose veins associated with perforating veins in 44.7%. The most common IPV was the Cockett perforator (connecting with the posterior tibial veins), accounting for 25.8% [7].

Contemporary methods of closing IPVs include: surgical ligation, using laser energy, high-frequency radio waves, sclerotherapy and fast-polymerisation cyanoacrylate glue (n-butyl-2-cyanoacrylate) (CA). In the past, cruroscopy and subfascial ligation of varicose veins were used; however, the role of SEPS (subfascial endoscopic perforator surgery) in the treatment. Only low or very low-certainty evidence was available for inclusion [8]. The first publication on the use of CA in the treatment of chronic venous insufficiency appeared in 2013 [9]. To evaluate the effectiveness of treating IPVs using chemical ablation with CA.

Material and methods

At JBS Phlebology Clinic in Gdansk and Lublin, out of 2,500 patients examined for chronic venous disease, 450 limbs had incompetent perforating veins. Among these, 132 isolated incompetent perforating veins were identified in 120 patients. An “isolated IPV” was defined as the absence of trunk incompetence during qualification. One person could present more than one incompetent perforating vein.

Patients were qualified for cyanoacrylate treatment if they met the following criteria:

• absence of truncal venous incompetence,
• absence of post-thrombotic changes,
• no previous sclerotherapy.

Incompetent perforating veins were located in the thigh, popliteal fossa and calf. Remaining incompetent perforating veins were qualified for sclerotherapy, ligation or observation. Very wide perforating veins, above 5 mm,
were referred for surgical ligation.

Exclusion criteria included: length > 2 cm, diameter > 5 mm (in standing position) and allergy. The glue used in procedures spreads approximately 1 cm and polymerises within 5 seconds upon contact with the vessel wall in a moist environment. For this reason, perforating veins chosen for treatment were not shorter than 2 cm.

Over 60% of the patients (84) had concomitant varicose – C2 according to CEAP (clinical-etiological-anatomical- patological) vein disease classification, over 50% (72 patients) had oedema (C3), and over 30% (45 patients) had previously experienced hyperpigmentation or varicose eczema (C4), all of whom had incompetent paratibial perforating veins. Patients with active ulcers did not qualify because the glue can trigger allergic reactions, and the skin surrounding an ulcer is highly sensitive.

All patients had symptoms of chronic venous disease – such as leg pain and heaviness – which had been resolved after we eliminated the reflux.

Written informed consent was obtained from all patients. All the patients were informed about potential side effects associated with the glue.

The patient’s choice of treatment was usually influenced by the following features: minimal invasiveness (single puncture), immediate effect and lack of requirement for compression stockings after the procedure. Each patient, when signing the informed consent for the procedure, was presented with other possible and available treatment methods.

The procedure consisted of a direct puncture of the IPV just above the fascia. A 25G 0.5 ^x 40 mm needle and a 2.5 ml Terumo syringe with low silicone content were used. After visualising the needle tip on the ultrasound image, 0.2–0.3 ml of CA was administered. Blood aspiration into the needle and syringe should be avoided, as it may cause premature polymerisation of CA within the needle or syringe. In IPVs exceeding 4 mm, 0.9% NaCl was injected subfascially immediately prior to glue administration to reduce vein diameter. Directly following CA injection, manual compression was applied for 3 minutes at the injection site. Post-procedural compression therapy using compression stockings was not required.

Venex cyanoacrylate glue from Vesta Medical was used. It is currently the only glue approved in Poland for PV treatment CE (Conformite Europeenne) certificate or Declaration of Conformity – i.e., European Union product certification.

Follow-up clinical examination and duplex ultrasound were performed after 4 and 8 weeks.

These are short-term results. Further prospective studies with larger patient populations and longer follow-up periods are necessary to evaluate the long-term durability of vein closure and recurrence rates.

Statistics

Because several cells in the contingency table contained expected frequencies below five, the association between anatomical location and treatment outcome was evaluated using the Fisher-Freeman-Halton exact test (an extension of Fisher’s exact test for r ^x c contingency tables). Pairwise comparisons between anatomical locations were subsequently performed using Fisher’s exact test with Bonferroni correction for multiple testing.

Results

All treated IPVs were either completely occluded or significantly narrowed (Figure 1).

The results were divided into two groups:

• complete occlusion – successful outcome – 115 (87%) cases,
• narrowing without reflux – satisfactory result – 17 (13%) cases.

Table 1 summarises the number of perforating veins treated, treatment outcomes (closed or narrowed) and the success rate for each location. The global Fisher-Freeman-Halton exact test demonstrated a statistically significant association between anatomical location and treatment outcome (p = 0.0153).

In the statistical analysis, the pairwise comparisons between anatomical locations remained statistically non-significant. This finding is most likely attributable to the small sample sizes within several anatomical subgroups, resulting in limited statistical power (Figure 2).

Therefore, differences between anatomical locations should be interpreted with caution and regarded primarily as descriptive observations rather than definitive evidence of differences in treatment effectiveness. The lowest success rate was observed in popliteal fossa perforating veins (33.3%). However, this subgroup included only a small number of treated veins because treatment in this region was abandoned for anatomical reasons, including the location of a perforating vein in the popliteal fossa, constant leg flexion, the potential risk of glue migration, and the proximity of large deep veins (the popliteal vein). The low success rate should be attributed to the small sample size. The highest success rates were observed for perforating veins located just above the knee (medial knee – 100%) and in the thigh (medial thigh and posterior thigh – both 100%). Differences between the groups are illustrated in bar charts. None of the perforating veins closed at the 4-week follow-up showed recanalisation at 8 weeks (Figure 3).

Procedure adverse events

Needle clogging occurred during three procedures, most likely due to unintentional microaspiration of blood. 40% of patients reported a transient burning sensation immediately after the glue was administered, which subsided within 3 minutes of compression. In one case, the burning sensation persisted for approximately one hour. In 24% of cases, the post-procedural complaint was a “pulling sensation” at the injection site, not described as pain. Potential adverse events listed in the manufacturer’s instructions for Venex include: urticaria, asthma, pollinosis and allergic reactions to cyanoacrylate like anaphylactic shock, arteriovenous fistula, arteriovenous fistula, infection and haemorrhage in entrance area, deep venous thrombosis, oedema, embolism including pulmonary embolism, hyperpigmentation, non-specific light irritancy, pain, paraesthesia, phlebitis, superficial thrombophlebitis, tearing of vein, perforation and scar formation at the injection site. Longer follow-up is required to assess the results and potential late complications, including granulomatosis. However, the risk appears low considering the very small volume of glue used. All patients had DUS of deep and superficial veins performed before treatment and at 4- and 8-week follow-up. No cases of deep vein thrombosis or superficial vein thrombosis were diagnosed.

Discussion

Incompetent perforating veins are relatively difficult to treat effectively, which explains why no currently available method achieves both 100% efficacy and minimal invasiveness [7, 9, 10].

Surgical ligation of IPVs is an inexpensive and relatively simple technique; however, it is more invasive than a single-puncture procedure because local anaesthesia, skin incision, and suturing are required. In addition, special attention must be paid not to leave a venous stump above the fascia, which may contribute to recurrence [11, 12].

Sclerotherapy is also a simple and widely used method. However, since foam may readily migrate into the deep venous system, where faster blood flow destabilises the sclerosant, recanalisation and the risk of foam entering
the deep system are more frequent [10, 13].

Radiofrequency and endovenous laser thermal ablation are effective techniques with high occlusion rates, but they are associated with substantially higher procedural costs, the need for tumescent anaesthesia, and greater procedural complexity.

Cyanoacrylate closure appears to be a good alternative – minimally invasive, effective and less expensive. Nevertheless, there is still a role for surgical treatment based on perforating vein anatomy, including width, length, diameter, and the presence of trophic changes [10, 14].

In this study, cyanoacrylate chemical ablation achieved technical success in all treated veins, with either complete closure (87%) or significant narrowing without reflux (13%). Furthermore, no early recanalisation was observed, indicating good short-term durability of the treatment effect. The lowest efficacy was observed in popliteal fossa perforating veins, whereas the highest efficacy was achieved in perforating veins located around the knee and thigh.

Although the global Fisher-Freeman-Halton exact test indicated an association between anatomical location and treatment outcome, no statistically significant differences were observed in pairwise comparisons after Bonferroni correction. This discrepancy is most likely related to the limited number of observations within several anatomical subgroups, resulting in insufficient statistical power. Consequently, the observed location-specific differences should be interpreted with caution.

The clinical outcome was favourable, as the procedure was well tolerated with only minor and transient adverse effects. No major complications associated with glue administration or deep venous extension occurred.

Compared with other minimally invasive methods for IPV treatment, cyanoacrylate ablation offers several practical advantages, including a single puncture technique, avoidance of thermal injury and tumescent anaesthesia, immediate vein occlusion, and the lack of requirement for post-procedural compression therapy. These features may improve patient comfort and simplify outpatient management. In selected patients, the method may therefore represent an attractive alternative to thermal ablation or surgical ligation while maintaining high short-term effectiveness.

A limitation of this study is that 132 perforating veins were analysed in 120 patients, indicating that a small number of patients contributed more than one treated vein. Consequently, complete independence of observations cannot be assumed. Because only a small proportion of patients contributed multiple observations, this issue is unlikely to have substantially influenced the overall findings. However, the statistical results should be interpreted with caution. Future studies should apply statistical models that account for within-patient clustering, such as mixed-effects models or generalised estimating equations.

However, careful patient qualification remains essential, particularly regarding perforating vein diameter, length, location, and trophic skin changes. Larger prospective studies with extended follow-up periods are necessary to compare the long-term durability of vein closure and recurrence rates with other established methods.

Conclusions

Cyanoacrylate chemical ablation of IPVs is a promising, minimally invasive, safe and effective outpatient treatment, however careful patient selection is required.

Further prospective studies with larger patient populations and longer follow-up periods are required to evaluate the long-term durability of vein closure and recurrence rates in comparison with other established methods for the treatment of perforating vein insufficiency.

References