Pathogenesis and etiology of recurrent varicose

veins
Maresa Brake, MBBS, BSc, Chung S. Lim, MRCS, PhD, Amanda C. Shepherd, MRCS, MD,
Joseph Shalhoub, MRCS, PhD, and Alun H. Davies, DM, FRCS, London, United Kingdom

Background: Recurrent varicose veins (RVV) occur in 13% to 65% of patients following treatment, and remain a debili-
tating and costly problem. RVV were initially thought largely to be due to inadequate intervention, however, more
recently neovascularization and other factors have been implicated. This review aims to provide an overview of the current
understanding of the etiology and pathogenesis of RVV.
Methods: A systematic search of the PubMed database was performed using the search terms including “recurrent,”
“varicose veins,” and “neovascularization.”
Results: Three types of RVV have been reported, namely residual veins, true RVV, and new varicose veins, although the
definitions varied between studies. RVV are attributable to causes including inadequate treatment, disease progression,
and neovascularization. Using duplex ultrasonography, neovascularization has been observed in 25% to 94% of RVV.
These new vessels appear in various size, number, and tortuosity, and they reconnect previously treated diseased veins to
the lower limb venous circulation. Histologically, these vessels appear primitive with incomplete vein wall formation,
decreased elastic component, and lack of valves and accompanying nerves. Although the rate of RVV following open
surgery and endovenous treatment appears similar, neovascularization seems less common following endothermal abla-
tion. Other causes of RVV following endovenous treatment include recanalization and opening of collaterals.
Conclusions: Recurrence remains poorly understood following treatment of varicose veins. Neovascularization is an
established and common cause of RVV, although other factors may contribute. (J Vasc Surg 2013;57:860-8.)

Open surgery remains the most common varicose vein
intervention at present in the United Kingdom; approxi-
mately 24,000 operations are carried out annually.1,2 Mini-
mally invasive treatments including endovenous thermal
ablation and ultrasound-guided foam sclerotherapy (UGFS)
are becoming increasingly popular.3 Despite advances in,
and increased availability of, pre- and perioperative investiga-
tion such as duplex ultrasonography, recurrence rates
following varicose veins treatment remain relatively high.4
Recurrent varicose veins (RVV) have been reported to occur
in 7% to 65% of patients following treatment5-8 and remain
a common, debilitating, complex, and costly problem.9,10
Treatment for RVV is technically more difficult to perform6
and patient satisfaction is poorer than after primary
interventions.11
Despite their frequent occurrence, the etiology and
pathogenesis of RVV remain incompletely understood.
RVV were initially thought to be largely due to inadequate
surgery especially when procedures were often performed
by junior surgeons, leaving remnants of diseased great
saphenous vein (GSV) or tributaries that enlarged with
time, or the development of varicosities in collateral
veins.12 More recently, other factors including neovascula-
rization have been shown to contribute to RVV following
surgery.13,14 Furthermore, the factors leading to the devel-
opment of RVV following endovenous ablation and sclero-
therapy may be different from those after open surgery.
The aim of this review was to provide an overview of the
current understanding and ongoing debate regarding the
etiology and pathogenesis of RVV.
METHODS
A systematic literature search of the PubMed database
was performed for articles about the etiology and patho-
genesis of RVV (Fig 1). Appropriate search terms were
employed, including “recurrent,” “varicose veins,” and
“neovascularization.” Only articles written in English
were included. Results from animal studies were excluded.
The search was expanded by scrutinizing the references of
articles identified for further relevant papers.

DEFINITIONS AND CLASSIFICATION OF RVV

From the Academic Section of Vascular Surgery, Department of Surgery
and Cancer, Charing Cross Hospital, Imperial College London.
Author conflict of interest: none.
Reprint requests: Alun H. Davies, DM, FRCS, Academic Section of Vascular
Surgery, Department of Surgery and Cancer, Charing Cross Hospital,
Imperial College London, 4 East, Fulham Palace Road, London W6
8RF, UK (e-mail: a.h.davies@imperial.ac.uk).
The editors and reviewers of this article have no relevant financial relationships
to disclose per the JVS policy that requires reviewers to decline review of any
manuscript for which they may have a conflict of interest.
0741-5214/$36.00
Copyright Ó 2013 by the Society for Vascular Surgery.
http://dx.doi.org/10.1016/j.jvs.2012.10.102
The definitions of RVV may vary. Three types of RVV
have been described.10 First, residual varicose veins are
those which were already present in operated sites at
1-month follow-up, left as a result of tactical or technical
error. Second are true RVV, which are absent at 1-month
follow-up but subsequently appear either as a result of neo-
vascularization or as a result of tactical or technical error.
Third are new varicose veins, which were not present at
1-month follow-up but develop later in untreated areas
due to disease progression.

860
JOURNAL OF VASCULAR SURGERY
Volume 57, Number 3 Brake et al 861

Number of articles identified by

search strategy
n = 1439 Articles excluded
Non-English n = 496
Animal studies n = 43
Duplicates n = 18
Potentially relevant articles identified
for title screening
n = 882
Articles excluded based
on title screen
n = 793
Potentially relevant articles identified
for abstract screening
n = 89
Articles excluded based
on abstract screen
n = 43
Potentially relevant articles retrieved
for more detailed evaluation Articles added from reference lists
n = 46 of articles reviewed
n=5

Articles excluded
Articles identified for inclusion in No discussion of aetiology or
review pathogenesis of recurrent varicose
n = 26 veins n = 25

Fig 1. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) diagram.

RVV can also be classified into radiologic and clinical; Table. Four major sources of recurrence following
importantly, radiologic recurrence does not necessarily varicose vein surgery (adapted from Kostas et al, 2004)
translate into clinical recurrence. For example, in a prospec-
tive study of UGFS in the treatment of GSV reflux in 203 Causes Explanation
legs (146 patients), the 5-year clinical recurrence was re-
Tactical error The persistence of venous reflux in
ported to be 4%, whereas duplex ultrasound recurrence a saphenous trunk resulting from
was 64%.15 Certain positive ultrasound findings suggest erroneous or inadequate preoperative
an increased risk of development of clinical RVV and reop- evaluation and inappropriate surgery
eration in future. In one study, patients with audible reflux Technical error The persistence of venous reflux
due to inadequate or incomplete
in the groin on a hand-held Doppler 1 year after open
surgical technique
surgery were found to have an increased risk of clinical Disease progression As a result of the natural history and
recurrence after 2 years.8 evolution of the disease
An international consensus meeting held on ‘recurrent Neovascularization The presence of reflux in previously
varices after surgery’ (REVAS) in Paris in 1998 agreed to ligated saphenofemoral junctions
cause by development of thin
adopt a clinical definition: the existence of varicose veins in incompetent serpentine veins linked
a lower limb previously operated on for varicosities, with or with a thigh varicosity
without adjuvant therapies, which includes true recurrences,
residual veins and new varices, as a result of disease progres-
sion.16-18 The four major causes of RVV following treat-
ment are shown in the Table.10 Using the REVAS presentation was found in 17%. In 35% of cases, the cause of
criteria, following open surgery RVV have been reported reflux was uncertain.18 When recurrence occurred at
at rates ranging from 6.6% to 37% after 2 years and up to a different site, development of reflux in new sites was found
51% after 5 years.14 Most patients with RVV were symp- in 32% of legs.18
tomatic, with various clinical presentations. Most had
uncomplicated varicose veins and swelling (70.9%), but ETIOLOGY OF RVV
the remainder had skin changes (29.1%).18 There were
multiple sources of reflux feeding the recurrence, though Tactical and technical error
incompetence at the saphenofemoral junction (SFJ) was RVV caused by tactical and technical error are attribut-
present in almost half of the patients. Ten percent had no able to inappropriate or inadequate treatment, respectively.
apparent source of reflux; in 17%, it was of pelvic or abdom- Tactical and technical errors were historically reported
inal origin. About 75% of legs had incompetent perforator to be the major cause of RVV, contributing up to 80%
veins.18 Neovascularization (20%) was as frequent as tech- of recurrences although this is likely to be untrue and
nical failure (19%) and tactical error (10%), and a combined outdated.6,19-24

862 Brake et al
Tactical error may arise from failure to identify the
source of reflux or all the incompetent veins requiring treat-
ment.25 Expansion of collateral veins may also contribute to
recurrent junctional incompetence.19-21,26 The increasing
use of duplex ultrasonography pre- and perioperatively
during open surgery, endothermal ablation, and UGFS is
likely to reduce the rate of tactical errors.25
The risk of RVV may increase if the GSV is not stripped
at all, or inadequately, although this remains controversial.5
In a randomized trial of 100 patients (133 legs) who
underwent SFJ ligation with or without GSV stripping,
Jones et al demonstrated a clinical recurrence rate at 2 years
of 43% after surgical ligation alone and 25% after ligation
and stripping, although 89% of the patients remained satis-
fied.5 Reoperation was required for 20 of 69 legs that
underwent ligation only, compared with 7 of 64 legs that
had additional GSV stripping (P ¼ .012).5 In endovenous
treatment, ablation of the GSV to the ankle opposed to
above-the-knee, appears to produce more favorable clinical
results, with greater improvement in quality of life, and
reduced recurrence.27 However, treating below-knee
GSV may also increase the rate of complications including
paresthesia.28 Therefore, further studies are needed to
determine which patients will benefit from full length treat-
ment of the GSV.
In contrast to the above, there is recently some
evidence to support that selective treatment of key points
of venous reflux, and preservation of the saphenous vein
may have a role to improve the efficacy of therapy and
reduce risk of RVV. Examples of such treatment include
the CHIVA (cure conservatrice et hémodynamique de l’in-
suffisance veineuse en ambulatiore or ambulatory conserva-
tive hemodynamic management) and ASVAL (ablation
sélective des varices sous anesthésie locale or ambulatory selec-
tive varicose vein ablation under local anesthesia of varicose
veins) techniques.14 In the CHIVA technique, following
careful duplex mapping, the clinicians perform flush liga-
tions at key points of venous reflux to decrease the hydro-
static pressure and preserve the superficial venous drainage
in the saphenous veins and tributaries. There is some
evidence from prospective studies including randomized
trials that the CHIVA technique is efficacious with compa-
rable, if not lower, rate of RVV.29-32 Meanwhile, the
ASVAL technique involves the treatment of the refluxing
epifascial veins while preserving the saphenous vein in
patients whom the clinicians judge that the reflux would
progress in the anterograde fashion.33 A retrospective study
by Pittaluga and colleagues has reported good outcomes in
patients with relatively less severe primary varicose veins.33
At present, both techniques should only be carried out on
selective patients by trained specialists.14 Further larger
randomized controlled trials are needed to confirm the effi-
cacy and safety of these techniques.
Inexperienced surgeons. Although there is no doubt
inexperienced surgeons are more prone to tactical or tech-
nical errors, and therefore increased risk of RVV, the claim
that this is the main cause of RVV has been disputed. Kos-
tas10 cited inadequate surgery as the least common etiology
JOURNAL OF VASCULAR SURGERY
March 2013
of recurrence (11%). A retrospective clinical follow-up
study from Sweden34 examined 100 legs from 89
patients who had primary SFJ ligation and stripping of the
GSV, and re-examined them after 6 to 10 years with duplex
imaging and varicography in some cases. There was no
significant difference in the recurrence rates related to the
surgeon’s experience: surgical resident (52%), general
surgeon (54%), and vascular surgeon (65%).
Recanalization and collateralization. Endovenous
ablation treatment and sclerotherapy cause obliteration of
the refluxing axial veins through thermal (laser or radiofre-
quency) energy or chemical irritation. A major cause of
RVV following endovenous ablation and sclerotherapy is
recanalization of the diseased veins. Although recanaliza-
tion is often reported as an outcome following endovenous
treatment, studies have suggested that it does not
necessarily result in clinical recurrence or symptomatic
reflux.28,35 The degree of damage to the vein wall required
for long-term occlusion is also unknown. Recanalization
can be reduced by improving the technical aspects of treat-
ment. For example, delivering at least 70 joules per cm of
laser energy to the vein wall reduces recanalization rates
following thermal ablation with short wavelength laser
(810 and 980 nm).36 Similarly, in endovenous radio-
frequency ablation, adequate pullback speed to ensure
proper thermal dose delivery during the procedure has been
shown to reduce the rates of recanalization of saphenous
veins.28 Recanalization is related to a number of factors,
including the vein diameter in addition to the energy
delivered. Similarly, in sclerotherapy, several technical
factors including the use of foam rather than liquid scle-
rotherapy, and injecting a higher volume of foam in larger
veins may reduce the rate of RVV.
Disease progression
This type of recurrence is attributable to the evolution
or persistence of varicosities derived from incompetence in
a remote or second saphenous system; usually the small
saphenous vein (SSV) is affected following previous surgery
to the GSV.37 The affected veins are clinically not varicose
at the time of treatment but later become refluxing as
a result of the natural history of the disease. It is well
known that primary varicose veins progress both in severity
and distribution over time.38,39 Disease progression is re-
ported to account for 20% to 25% of recurrences.37-39
Neovascularization
Neovascularization refers to new blood vessel forma-
tion, which can occur in an abnormal tissue or position.18
These new vessels arise in the granulation tissue along the
track of previously stripped or ligated veins.18,26 They
form between the common femoral vein, the residual GSV
stump, or its tributaries, and reconnect the incompetent
veins to the superficial venous circulation of the leg.26 These
new blood vessels are found relatively frequently, even after
correct functional ligation. Neovascularization has been re-
ported to account for 8% to 60% of RVV10,18,40-43 and is the
most common cause of recurrence, together with the
JOURNAL OF VASCULAR SURGERY
Volume 57, Number 3
Fig 2. The factors involved in the pathogenesis of true recurrence of varicose veins. The postulated factors contributing
to true varicose vein recurrence may broadly be divided into two groups: intraoperative factors (A) and postoperative
factors (B). CFV, Common femoral vein; GSV, great saphenous vein; SFJ, saphenofemoral junction.
development of varicose veins attributable to disease
progression in many studies.5,9,10,24,44,45
RVV secondary to neovascularization seem to be more
common after open surgery than endovenous treatment or
sclerotherapy. It contributed to 18% of the recurrences
following open surgery compared with only 1% to 1.5%
following endovenous treatment; yet, the overall rate of
RVV was similar after both treatments after 2-year
follow-up.13,46 In a prospective 5-year study of radiofre-
quency ablation for GSV reflux, neovascularization was
not detected in the follow-up. Endothermal ablation tech-
niques seldom result in hematoma or spillage of endothelial
cells as part of the procedure, which may be the origin of
neovascularization.47
Physiological and pathologic neovascularization.
Neovascularization is thought to be pathologic angiogen-
esis.48 Angiogenesis is the sprouting and expansion of
new blood vessels from existing vessels. Various mediators
are involved, including growth factors, matrix metal-
loproteinases and their tissue inhibitors, hypoxia-inducible
factors, and angiopoietin.49 Important growth factors
that have been implicated in neovascularization include
vascular endothelial growth factor, basic fibroblast growth
factors, and platelet-derived growth factor.49 Several
factors including hypoxia, mechanical stress, and inflam-
mation are known to stimulate angiogenesis,49 which may
be both physiological and pathologic.
The mechanisms responsible for neovascularization in
RVV remain unclear. It is thought that neovascularization
first develops months or even years after the initial opera-
tion.50 It may be induced by diffusible angiogenic factors18
released from the surrounding tissues. Physical factors that
have been implicated include the type of suture material
Brake et al 863
used to ligate the GSV stump, exposure to free stump
endothelium,51 hemodynamic effects,52 operative trauma,
and thrombosis53 (Fig 2). Several hypotheses have been
postulated to explain the development of neovascularization
following varicose vein surgery. First, neovascularization
may be a physiological response to venous disconnection.
Second, it may be a manifestation of the effect of altered
venous hemodynamics in a system of susceptible veins.24
Third, neovascularization may be part of the normal
sequence of wound healing, originating from hypoxia-
induced activation of endothelial cells distal to the stump
ligature leading to the release of angiogenic factors.54
Fourth, the track of the previously stripped vein may recan-
alize and endothelialize. Neovascularization may be associ-
ated with hematoma formation following the initial
surgery, but this has not yet been assessed.55
Imaging neovascularization. On venography and
duplex ultrasonography, neovascularization appears as
a complex network of tortuous vessels (Fig 3) reconnecting
the proximal or distal cut ends of the GSV or one of its
tributaries to the femoral vein.24 The appearance is different
from residual varicose veins (or non-varicose),8 and neo-
vascular veins are observed after 25% to 94% of
RVV.5,9,10,12,13,39,45,56 Duplex ultrasonography and venog-
raphy are limited by their inability to differentiate
true neovascularization from the dilatation of existing
collateral veins as they appear similar.8,40,42,57 New veins
seen on clinical imaging may represent adaptive dilation of
pre-existing venous channels in response to abnormal
hemodynamic forces, rather than true neovascularization.57
Histology and resin casting. The morphology of
neovascularization has been studied using resin casts and
histologic analysis including immunohistochemistry. In

864 Brake et al
Fig 3. Neovascularization (blue and red) around a previously
ligated saphenofemoral junction of a patient with recurrent vari-
cosities on color duplex ultrasonography.
the 1980s, Glass conducted an early histologic study that
found continuity of a ligated vein was restored by growth
of new vessels in the surrounding tissue and vein wall.18
Resin casts clearly illustrate the tortuosity and extent of
the neovascularization as well as the variation in size of the
veins (Fig 4).41 The direction of the neovascularization
channels from the stump is always outwards toward the
subcutaneous tissue.54 Some of these new vessels reconnect
with the main venous tributaries and establish channels of
sufficient caliber to become clinical recurrences.54
Histologically, neovascular vessels appear primitive and
immature, with incomplete vein wall formation, no valves,
and a lack of clearly define tunica intima, media, and adven-
titia. The vessel wall appears asymmetrical and thinner than
normal vein. Most of these vessels are either composed of
squamous endothelium only or lined by few layers of
vascular smooth muscle cells. No intimal thickening is
observed and the vein wall lacks elastic fibers. In 80% no
capillaries or vasa vasorum are detected in the vascular
wall. Scar tissue is often seen around the vessel.58
Blood vessels generally contain nerve fibrils, which
express S100 protein, particularly S100A1 and S100B.
Neovascularization in RVV is characterized by an incom-
plete vessel wall lacking intramural nerves on S100 staining,
a feature similar to the immature neovessels seen in granu-
lation tissue and tumor.42 One study identified histologic
evidence of neovascularization in 94% of RVV, all of which
stained negative for S100.59 Other markers that have been
used to identify neovascularization include Mib1, a mono-
clonal antibody that recognizes proliferating cells by
binding to Ki-67.57
Although many of the features observed in histologic
studies support neovascularization as an important cause
of RVV, other studies have disputed this. Using immunohis-
tochemistry, El Wajeh et al found S100 positive nerve fibrils
in the majority of dilated vascular channels from both their
patients having redo varicose vein surgery and control
groups.57 They found little evidence of neovascularization
JOURNAL OF VASCULAR SURGERY
March 2013
Fig 4. Resin casts of recurrent refluxing saphenofemoral junction
specimens. Following injection of resin from the saphenofemoral
junction, a tortuous network of vessels is visualized. There is a vari-
ation in size and abundance of vessels when comparing both spec-
imens (A and B). The direction of the neovascularization channels
was noted to be outward from the stump toward the subcutaneous
tissue. A, Several larger channels are accompanied by many much
smaller channels running in a proximal to distal direction. B, This
cast is dominated by three large-diameter tortuous channels, with
a number of small channels present in continuity. Scale bars:
(A) 5 mm; (B) 10 mm. (This image has been reproduced with
permission from the Journal of Vascular Surgery.)41
associated with RVV and concluded that the venous chan-
nels that develop at the previously ligated SFJ may represent
an adaptive dilatation of pre-existing venous channels and
vascular remodelling, in response to abnormal hemody-
namic forces.45
COMPARISON OF RVV BETWEEN TREATMENT
MODALITIES
A meta-analysis of endovenous treatments for varicose
veins found that endovenous laser ablation demonstrated
significantly better occlusion rate, although this may not
necessarily translate into clinical recurrences, than stripping,
UGFS, and radiofrequency ablation.60 The 5-year vein
occlusion rate for endovenous laser ablation (EVLA) was
95.4% compared with 79.9% with the original radiofre-
quency ablation (RFA) catheters, however, the latest radio-
frequency devices deliver a higher energy and medium- and
long-term outcome data for these new devices is awaited.61
Stripping and UGFS have reported 5-year success rates of
75.7% and 73.5%, respectively.60 The long-term results
of all forms of treatment may depend on the rates of
neovascularization.13,60 However, despite apparent reduc-
tions in neovascularization and excellent occlusion rates,
JOURNAL OF VASCULAR SURGERY
Volume 57, Number 3
randomized clinical trials comparing EVLA and stripping
have failed to show a significant advantage of laser at 2 years
in terms of recurrence and quality of life outcomes.25,62
Clinical trials comparing stripping and RFA have shown
advantages in quality of life for RFA at 2 years.46
Clinical studies comparing UGFS with surgery and
thermal ablation suggest that foam sclerotherapy is less
effective than surgery60,63 and EVLA,60 although long-
term evidence from randomized controlled trials is scarce.
The VEDICO trial (Foam-Sclerotherapy, Surgery, Sclero-
therapy, and Combined Treatment for Varicose Veins: A
10-Year, Prospective, Randomized, Controlled, Trial)
showed that low dose sclerotherapy was less effective than
high dose; results were worse with highly diluted or undi-
luted 3% sclerosant compared with a 1.5% concentration.63
Rates of RVV after 5 years were 44% for UGFS, rising to
56% after 10 years.
Whereas short-term data after new endothermal tech-
niques are plentiful,56 long-term outcome data concerning
recurrence and quality of life are currently awaited. A
number of appropriately powered studies will report results
in the next few years.25,64,65
DISCUSSION
There have been a number of recent advances in the
treatment of varicose veins, including the increasing use
of duplex ultrasonography, treatment by specialists, and
new endovenous therapies. Yet, the recurrence rates after
treatment remain a challenge, at least partly because of
a lack of understanding of the pathogenesis and etiology
of RVV. The definition of RVV often varies in studies. In
some, residual veins are included as RVV whereas others
consider them not strictly RVV. Understanding the mech-
anisms of recurrence is essential for the development of
preventative and therapeutic strategies.
SFJ reflux is caused by incompetence of one or more of
the axial veins or tributaries arising from it. Therefore,
during treatment of varicose veins, regardless of technique,
all tributaries of the SFJ or proximal GSV with demon-
strated reflux require obliteration to prevent recurrence.
Most patients (85%) with SFJ incompetence only have
GSV reflux.66 Traditional teaching suggests all tributaries
or axial veins arising from the SFJ should be ligated at
open surgery, despite the lack of evidence that this reduces
recurrence and neovascularization. Endovenous thermal
ablation techniques obliterate axial vein reflux but do not
specifically interrupt the proximal SFJ tributaries. Theivacu-
mar and colleagues assessed 81 legs (70 patients) 12 months
after EVLA of the GSV and found that none of the legs
showed SFJ reflux, although one or more patent tributaries
were visible in 48 (59%) patients. The authors concluded
that persistent nonrefluxing GSV tributaries at the SFJ did
not appear to have an adverse effect on clinical outcome 1
year after successful EVLA of the GSV.66 However, in
another study, several cases of new reflux in the anterior
accessory vein were found 2 years after EVLA.25 The obser-
vation time in randomized trials comparing RVV after
endovenous treatment vs surgery is still relatively short,
Brake et al 865
therefore, no firm conclusion can be drawn regarding differ-
ences in RVV and neovascularization.
Meanwhile, the treatment of the competent GSV in
patients with an isolated refluxing anterior accessory great
saphenous vein (AAGSV), which may occur in 10% of
patients with SFJ reflux, is also unclear. Theivacumar and
colleagues studied 30 patients who underwent AAGSV
laser ablation alone and 33 age/sex-matched controls
undergoing GSV laser ablation. The authors concluded
that GSV-sparing laser ablation of the AAGSV abolishes
SFJ reflux associated with isolated SFJ/AAGSV reflux
and improves symptom scores and patient satisfaction to
a similar extent as GSV laser ablation, with no evidence
of new GSV reflux or recurrent varicosities at 1-year
follow-up.67 Because of lack of long-term data, the optimal
treatment of AAGSV remains unclear. Some clinicians
advocate for primary ablation of the AAGSV even if it is
competent at the initial treatment because of potentially
relatively high incidence of late reflux in this vein.25
However, some clinicians have suggested avoiding ablation
of this vein at the initial operation66,68 because it can be
treated at a later stage should it become incompetent,
resulting in the development of RVV.25
Neovascularization is accepted by most vascular
surgeons as an established cause of RVV, especially following
open surgery. Despite this, several problems remain
including the lack of a unifying definition which makes
assessment and reporting difficult. It is difficult to be confi-
dent that all the neovascularization described in the litera-
ture was true neovascularization, which may explain some
of the conflicting results reported by various studies. For
example, one study considered all veins joining the GSV
stump or junctional area as missed tributaries,40 whereas
other studies considered stump tributaries as substantial as
3 mm in diameter to be consistent with neovascularization.
Another problem is that few studies have correlated imaging
findings to histologic evidence, thereby making the inter-
pretation of neovascularization more variable and less
convincing. There is a lack of knowledge pertaining to the
molecular biology of neovascularization despite the advance-
ment in this area in other clinical contexts.
Increasingly, research is being undertaken to develop
effective strategies to prevent and treat RVV; neovasculari-
zation, therefore, is an important target. Various surgical
techniques have been compared with elucidate which
have more favorable outcomes, including lower rates of
recurrence and neovascularization.69 One important study
compared the long-term clinical advantages of ligation of
SFJ with and without GSV stripping during routine
primary varicose vein surgery.70 Although neovasculariz-
ation was present in both groups, stripping reduced the
need for reoperation by two-thirds at 5 years.70 Another
study compared traditional surgical treatment for varicose
vein recurrence, which involved removing all sources of
reflux from the deep venous network with the superficial
venous network, with a less aggressive surgical approach
focusing on treatment of the varicose reservoir and avoid-
ing redo surgery at the groin. Postoperative complications

866 Brake et al
were 6.7% and 0.5%, respectively. After 3-year follow-up,
traditional surgery had a recurrence rate of 9.2%, whereas
recurrence in the second group was 7.1%.33
The conservative approach to surgical varicose vein
treatment, the CHIVA and ASVAL methods, show that
selective surgical treatment may be a viable option.29,33,69,71
Studies have shown that RVV occur more frequently
following saphenous stripping than after CHIVA treat-
ment.29,71 One study showed that recurrence rates are
halved at 10 years following CHIVA, with 35% recurrence
after stripping and 18% recurrence after CHIVA.29 Equally,
ASVAL showed good results with regard to neovasculariza-
tion, which was only seen in 0.9% of cases, and recurrence,
which was present in 6.3%.69
Other strategies to prevent neovascularization that
have been described include the use of a synthetic physical
barrier. These barriers include polytetrafluoroethylene and
silicone patch saphenoplasty, which involves suturing a pol-
ytetrafluoroethylene and silicone patch, respectively, over
the saphenous opening after flush saphenofemoral liga-
tion.56,72 This method has been deemed safe,56 and
a studies have reported an approximately 50%48,72 reduc-
tion in neovascularization, although further studies are
needed to confirm this before it can be used routinely.
Studies comparing endovenous treatment and open
surgery have already reported a reduction in neovasculari-
zation despite the overall RVV rate remaining similar in
both treatment arms, likely attributable to recanalization
and opening of collaterals.3,6,73 It is unclear why collaterals
do not open up after surgery as well as after endovenous
therapies. One possible explanation for this is that there
are still microchannels between the collaterals and the
treated veins, whereas in open surgery, the connections
between them are completely removed by either vein strip-
ping or avulsion. Therefore, improving our understanding
of RVV following endovenous therapies and refining the
technology including optimizing the efficiency of energy
delivery and targeting the right varicosities may have the
potential to reduce the overall rate of RVV.
In addition to applying and improving the currently
established treatment of varicose veins, the application of
pharmacologic agents that prevent neovascularization
may have a role in the future. For example, the local appli-
cation of inhibitors of angiogenesis during varicose vein
treatment is an attractive putative approach to prevent or
limit neovascularization. There are commercially available
angiogenesis inhibitors such as bevacizumab, an anti-
vascular endothelial growth factor biologic available for
the treatment of cancer.74 More selective angiogenesis
inhibitors are also being developed to reduce the side
effects and to improve the specificity of the treatment.
CONCLUSIONS
RVV remains a poorly understood pathology following
treatment of varicose veins. Several etiologic factors
including tactical and technical error, disease progression,
and neovascularization contribute to the development of
RVV. The factors contributing to the development may
JOURNAL OF VASCULAR SURGERY
March 2013
also vary with the type of varicose vein treatment. Addi-
tional molecular and clinical studies are required to under-
stand the pathophysiology of RVV further in the
development of more effective preventative and treatment
strategies.
AUTHOR CONTRIBUTIONS
Conception and design: MB, CL, JS, AS, AD
Analysis and interpretation: MB, CL, JS, AS, AD
Data collection: MB, CL, JS, AS, AD
Writing the article: MB, CL, JS, AS, AD
Critical revision of the article: MB, CL, JS, AS, AD
Final approval of the article: MB, CL, JS, AS, AD
Statistical analysis: Not applicable
Obtained funding: Not applicable
Overall responsibility: MB, CL, JS, AS, AD
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Submitted Mar 19, 2012; accepted Oct 22, 2012.