Treatment for telangiectasias and reticular veins

Luis CU Nakano; Daniel G Cacione; Jose CC Baptista-Silva; Ronald LG Flumignan

doi:10.1002/14651858.CD012723.pub2

. 2021 Oct 12;2021(10):CD012723. doi: 10.1002/14651858.CD012723.pub2

Treatment for telangiectasias and reticular veins

Luis CU Nakano ^1,^✉, Daniel G Cacione ¹, Jose CC Baptista-Silva ^1,², Ronald LG Flumignan ¹

Editor: Cochrane Vascular Group

PMCID: PMC8507602 PMID: 34637138

Abstract

Background

Telangiectasias (spider veins) and reticular veins on the lower limbs are very common, increase with age, and have been found in 41% of women. The cause is unknown and the patients may be asymptomatic or can report pain, burning or itching. Treatments include sclerotherapy, laser, intense pulsed light, microphlebectomy and thermoablation, but none is established as preferable.

Objectives

To assess the effects of sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy treatments for telangiectasias and reticular veins.

Search methods

The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, AMED and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 16 March 2021. We undertook additional searches in LILACS and IBECS databases, reference checking, and contacted specialists in the field, manufacturers and study authors to identify additional studies.

Selection criteria

We included randomised controlled trials (RCTs) and quasi‐RCTs that compared treatment methods such as sclerotherapy, laser therapy, intensive pulsed light, thermocoagulation, and microphlebectomy for telangiectasias and reticular veins in the lower limb. We included studies that compared individual treatment methods against placebo, or that compared different sclerosing agents, foam or laser treatment, or that used a combination of treatment methods.

Data collection and analysis

Three review authors independently performed study selection, extracted data, assessed risks of bias and assessed the certainty of evidence using GRADE. The outcomes of interest were resolution or improvement (or both) of telangiectasias, adverse events (including hyperpigmentation, matting), pain, recurrence, time to resolution, and quality of life.

Main results

We included 3632 participants from 35 RCTs. Studies compared a variety of sclerosing agents, laser treatment and compression. No studies investigated intensive pulsed light, thermocoagulation or microphlebectomy. None of the included studies assessed recurrence or time to resolution. Overall the risk of bias of the included studies was moderate. We downgraded the certainty of evidence to moderate or low because of clinical heterogeneity and imprecision due to the wide confidence intervals (CIs) and few participants for each comparison.

Any sclerosing agent versus placebo

There was moderate‐certainty evidence that sclerosing agents showed more resolution or improvement of telangiectasias compared to placebo (standard mean difference (SMD) 3.08, 95% CI 2.68 to 3.48; 4 studies, 613 participants/procedures), and more frequent adverse events: hyperpigmentation (risk ratio (RR) 11.88, 95% CI 4.54 to 31.09; 3 studies, 528 participants/procedures); matting (RR 4.06, 95% CI 1.28 to 12.84; 3 studies, 528 participants/procedures). There may be more pain experienced in the sclerosing‐agents group compared to placebo (SMD 0.70, 95% CI 0.06 to 1.34; 1 study, 40 participants; low‐certainty evidence).

Polidocanol versus any sclerosing agent

There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.01, 95% CI −0.13 to 0.14; 7 studies, 852 participants/procedures), hyperpigmentation (RR 0.94, 95% CI 0.62 to 1.43; 6 studies, 819 participants/procedures), or matting (RR 0.82, 95% CI 0.52 to 1.27; 7 studies, 859 participants/procedures), but there were fewer cases of pain (SMD −0.26, 95% CI −0.44 to −0.08; 5 studies, 480 participants/procedures) in the polidocanol group. All moderate‐certainty evidence.

Sodium tetradecyl sulphate (STS) versus any sclerosing agent

There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD −0.07, 95% CI −0.25 to 0.11; 4 studies, 473 participants/procedures). There was more hyperpigmentation (RR 1.71, 95% CI 1.10 to 2.64; 4 studies, 478 participants/procedures), matting (RR 2.10, 95% CI 1.14 to 3.85; 2 studies, 323 participants/procedures) and probably more pain (RR 1.49, 95% CI 0.99 to 2.25; 4 studies, 409 participants/procedures). All moderate‐certainty evidence.

Foam versus any sclerosing agent

There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD 0.04, 95% CI −0.26 to 0.34; 2 studies, 187 participants/procedures); hyperpigmentation (RR 2.12, 95% CI 0.44 to 10.23; 2 studies, 187 participants/procedures) or pain (SMD −0.10, 95% CI −0.44 to 0.24; 1 study, 147 participants/procedures). There may be more matting using foam (RR 6.12, 95% CI 1.04 to 35.98; 2 studies, 187 participants/procedures). All low‐certainty evidence.

Laser versus any sclerosing agent

There was no clear difference in resolution or improvement (or both) of telangiectasias (SMD −0.09, 95% CI −0.25 to 0.07; 5 studies, 593 participants/procedures), or matting (RR 1.00, 95% CI 0.46 to 2.19; 2 studies, 162 participants/procedures), and maybe less hyperpigmentation (RR 0.57, 95% CI 0.40 to 0.80; 4 studies, 262 participants/procedures) in the laser group. All moderate‐certainty evidence. High heterogeneity of the studies reporting on pain prevented pooling, and results were inconsistent (low‐certainty evidence).

Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol)

Low‐certainty evidence suggests there may be more resolution or improvement (or both) of telangiectasias in the combined group (SMD 5.68, 95% CI 5.14 to 6.23; 2 studies, 710 participants), and no clear difference in hyperpigmentation (RR 0.83, 95% CI 0.35 to 1.99; 2 studies, 656 participants) or matting (RR 0.83, 95% CI 0.21 to 3.28; 2 studies, 656 participants). There may be more pain in the combined group (RR 2.44, 95% CI 1.69 to 3.55; 1 study, 596 participants; low‐certainty evidence).

Authors' conclusions

Small numbers of studies and participants in each comparison limited our confidence in the evidence. Sclerosing agents were more effective than placebo for resolution or improvement of telangiectasias but also caused more adverse events (moderate‐certainty evidence), and may result in more pain (low‐certainty evidence). There was no evidence of a benefit in resolution or improvement for any sclerosant compared to another or to laser. There may be more resolution or improvement of telangiectasias in the combined laser and polidocanol group compared to polidocanol alone (low‐certainty evidence). There may be differences between treatments in adverse events and pain. Compared to other sclerosing agents polidocanol probably causes less pain; STS resulted in more hyperpigmentation, matting and probably pain; foam may cause more matting (low‐certainty evidence); laser treatment may result in less hyperpigmentation (moderate‐certainty evidence). Further well‐designed studies are required to provide evidence for other available treatments and important outcomes (such as recurrence, time to resolution and delayed adverse events); and to improve our confidence in the identified comparisons.

Keywords: Female, Humans, Pruritus, Pruritus/drug therapy, Sclerotherapy, Telangiectasis, Telangiectasis/therapy, Veins

Plain language summary

Treatment for telangiectasias and reticular veins

What are telangiectasias and reticular veins?

Telangiectasias (spider veins) are small dilated blood vessels near the skin surface measuring less than 1.0 mm in diameter. Reticular veins have a diameter of less than 3.0 mm and are deeper in the skin. The cause is unknown, and they can be solely cosmetic, or can result in pain, burning or itching. Telangiectasias and reticular veins on the legs are very common, increase with age, and have been found in 41% of women over the age of 50 years. Risk factors include family history, pregnancy, local trauma, obesity and hormonal factors

How are telangiectasias and reticular veins treated?

There are several treatments, such as sclerotherapy, laser, intense pulsed light, microphlebectomy and thermoablation, but none is established as preferable. Unwanted side effects of treatments include hyperpigmentation (skin darkening), matting (new telangiectasis after treatment), allergy and pain. It is therefore important to know the effects of these treatments to help doctors and patients decide which is the best option for them.

What did we do?

We searched for studies where patients were randomly selected to receive one treatment for spider veins compared to a sham treatment, or to another type of treatment. We then compared the results and summarised the evidence from all the studies. Finally, we assessed how certain we are of the evidence. We considered factors such as the way studies were conducted, study sizes, and consistency of findings across studies. Based on our assessments, we categorised the evidence as being of very low, low, moderate or high certainty.

What did we find?

We found 35 studies with a combined total of 3632 participants (searched to 16 March 2021). Some studies compared one treatment on one leg to another treatment on the other leg. Studies used a variety of different treatments and none of them reported on all of our outcomes. Not all available treatments were investigated: no studies investigated intensive pulsed light, thermocoagulation or microphlebectomy.

Sclerosing agents improved telangiectasias and reticular veins resolution when compared to sham treatment, but resulted in more unwanted side effects (hyperpigmentation and matting). There was no benefit seen in one sclerosing agent compared to another, or compared to laser, for improving telangiectasias. There may be differences between treatments in adverse events and pain. Compared to other agents, polidocanol may result in less pain. Sodium tetradecyl sulphate (STS) may cause more hyperpigmentation, matting and probably more pain; foam may result in more matting; laser treatment may cause less hyperpigmentation. Combined laser plus sclerotherapy may result in better resolution compared to only sclerotherapy, but may cause more pain.

How reliable are these results?

We are not very confident in these results. We downgraded the certainty of the evidence by one or two levels (from high to moderate or low). This was because of the differences in the designs of the studies, which meant that only small numbers of studies and participants provided information for each treatment comparison.

Conclusion

Further well‐designed studies are needed to improve our confidence in the comparisons identified in this review, for other treatments available, and for other important outcomes, such as recurrence, time to resolution and long‐term side effects.

Summary of findings

Summary of findings 1. Sclerotherapy compared to placebo for treatment of telangiectasias and reticular veins.

Sclerotherapy compared to placebo for treatment of telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: sclerotherapy (any) Comparison: placebo
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with placebo	Risk with sclerotherapy
Resolution or improvement of telangiectasias (follow‐up: 4 ‐ 12 weeks)		SMD 3.08 higher (2.68 higher to 3.48 higher)	‐	613 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 4 ‐ 12 weeks)	Study population		RR 11.88 (4.54 to 31.09)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
	25 per 1000	299 per 1000 (114 to 784)
Adverse events ‐ matting (follow‐up: 4 ‐ 12 weeks)	Study population		RR 4.06 (1.28 to 12.84)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
	17 per 1000	68 per 1000 (22 to 216)
Pain (follow‐up: 1 day)		SMD 0.7 higher (0.06 higher to 1.34 higher)	‐	40 (1 RCT)	⊕⊕⊝⊝ LOW^c	‐
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Sclerotherapy (polidocanol) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: sclerotherapy (polidocanol) Comparison: sclerotherapy (any sclerosant)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy (any sclerosant agent)	Risk with sclerotherapy (polidocanol)
Resolution or improvement of telangiectasias (follow‐up: 4 ‐ 16 weeks)		SMD 0.01 higher (0.13 lower to 0.14 higher)	‐	852 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 4 ‐ 16 weeks)	Study population		RR 0.94 (0.62 to 1.43)	819 (6 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	476 per 1000	447 per 1000 (295 to 680)
Adverse events ‐ matting (follow‐up: 4 ‐ 16 weeks)	Study population		RR 0.82 (0.52 to 1.27)	859 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	144 per 1000	118 per 1000 (75 to 183)
Pain (follow‐up: 1 day)		SMD 0.26 lower (0.44 lower to 0.08 lower)	‐	480 (5 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Sclerotherapy (STS) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: sclerotherapy (STS) Comparison: sclerotherapy (any sclerosant)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy (any sclerosant)	Risk with sclerotherapy (STS)
Resolution or improvement of telangiectasias (follow‐up: 4 ‐ 16 weeks)		SMD 0.07 lower (0.25 lower to 0.11 higher)	‐	473 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 4 ‐ 24 weeks)	Study population		RR 1.71 (1.10 to 2.64)	478 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	371 per 1000	634 per 1000 (408 to 979)
Adverse events ‐ matting (follow‐up: 4 ‐ 24 weeks)	Study population		RR 2.10 (1.14 to 3.85)	323 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	82 per 1000	173 per 1000 (94 to 318)
Pain (follow‐up: 1 day)	Study population		RR 1.49 (0.99 to 2.25)	409 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	275 per 1000	410 per 1000 (273 to 619)
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Sclerotherapy (hypertonic saline) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: sclerotherapy (hypertonic saline) Comparison: sclerotherapy (any sclerosant)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy (any sclerosant)	Risk with sclerotherapy (hypertonic saline)
Resolution or improvement of telangiectasias (follow‐up: 4 ‐ 12 weeks)	‐	SMD 0.01 higher (0.2 lower to 0.22 higher)	‐	348 (3 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 8 ‐ 12 weeks)	Study population		RR 0.74 (0.59 to 0.93)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
	493 per 1000	365 per 1000 (291 to 459)
Adverse events ‐ matting (follow‐up: 8 ‐ 12 weeks)	Study population		RR 0.89 (0.58 to 1.36)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
	215 per 1000	192 per 1000 (125 to 293)
Pain (follow‐up: 1 day)	‐	SMD 6.22 higher (5.7 higher to 6.73 higher)	‐	348 (3 RCTs)	⊕⊕⊕⊝ MODERATE^c	‐
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standard mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Sclerotherapy (chromated glycerin) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: sclerotherapy (chromated glycerin) Comparison: sclerotherapy (any sclerosant)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy (any sclerosing agent)	Risk with sclerotherapy (chromated glycerin)
Resolution or improvement of telangiectasias (follow‐up: 5 ‐ 24 weeks)	‐	SMD 0.45 higher (0.11 lower to 1.02 higher)	‐	125 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 5 ‐ 24 weeks)	Study population		RR 0.49 (0.09 to 2.50)	125 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
	66 per 1000	32 per 1000 (6 to 164)
Adverse events ‐ matting (follow‐up: 5 ‐ 24 weeks)	Study population		RR 0.31 (0.01 to 7.53)	99 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
	21 per 1000	6 per 1000 (0 to 157)
Pain (follow‐up: 1 day)	Study population		RR 1.50 (0.30 to 7.55)	26 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
	154 per 1000	231 per 1000 (46 to 1000)
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Foam compared to sclerotherapy (any sclerosant) for telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: foam Comparison: sclerotherapy (any sclerosant)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy (any sclerosing agent)	Risk with foam
Resolution or improvement of telangiectasias (follow‐up: 5 ‐ 10 weeks)	‐	SMD 0.04 higher (0.26 lower to 0.34 higher)	‐	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 5 ‐ 10 weeks)	Study population		RR 2.12 (0.44 to 10.23)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
	26 per 1000	55 per 1000 (11 to 265)
Adverse events ‐ matting (follow up: 5 ‐ 10 weeks)	Study population		RR 6.12 (1.04 to 35.98)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
	9 per 1000	53 per 1000 (9 to 310)
Pain (follow up: 1 day)		SMD 0.1 lower (0.44 lower to 0.24 higher)	‐	147 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Laser compared to sclerotherapy for treatment of telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: laser Comparison: sclerotherapy
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy	Risk with laser
Resolution or improvement of telangiectasias (follow‐up: 4 ‐ 24 weeks)	‐	SMD 0.09 lower (0.25 lower to 0.07 higher)	‐	593 (5 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 4 ‐ 24 weeks)	Study population		RR 0.57 (0.40 to 0.80)	262 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	328 per 1000	187 per 1000 (131 to 263)
Adverse events ‐ matting (follow‐up: 16 ‐ 24 weeks)	Study population		RR 1.00 (0.46 to 2.19)	162 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	123 per 1000	123 per 1000 (57 to 270)
Pain (follow‐up: 1 day)	Study population		‐	100 (2 RCTs)	⊕⊝⊝⊝ LOW^b	We were not able to pool the data due to high heterogeneity
	See comment	‐
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).  CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Laser plus sclerotherapy compared to sclerotherapy for treatment of telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: laser plus sclerotherapy Comparison: sclerotherapy
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*№ of participants/procedures^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy	Risk with laser plus sclerotherapy
Resolution or improvement of telangiectasias (follow‐up: 12 ‐ 16 weeks)	‐	SMD 5.68 higher (5.14 higher to 6.23 higher)	‐	710 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ Hyperpigmentation (follow‐up: 12 ‐ 16 weeks)	Study population		RR 0.83 (0.35 to 1.99)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
	64 per 1000	53 per 1000 (22 to 128)
Adverse events ‐ matting (follow‐up: 12 ‐ 16 weeks)	Study population		RR 0.83 (0.21 to 3.28)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
	18 per 1000	15 per 1000 (4 to 60)
Pain (follow‐up: 1 day)	Study population		RR 2.44 (1.69 to 3.55)	596 (1 RCT)	⊕⊕⊝⊝ LOW^b	‐
	266 per 1000	649 per 1000 (449 to 944)
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Sclerotherapy (hypertonic glucose plus polidocanol) compared with sclerotherapy (hypertonic glucose) for telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Settings: outpatient Intervention: sclerotherapy (hypertonic glucose plus POL) Comparison: sclerotherapy (hypertonic glucose)
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	*No of Participants^ (studies)**	Certainty of the evidence (GRADE)	Comments
	Risk with hypertonic glucose	Risk with hypertonic glucose plus POL
Resolution or improvement of telangiectasias (follow‐up: 12 ‐ 16 weeks)	‐	SMD 0.79 higher (0.50 higher to 1.09 higher)		191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ hyperpigmentation (follow‐up: 16 weeks)	Study population		RR 0.79 (0.62 to 1.01)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	649 per 1000	513 per 1000 (403 to 656)
Adverse events ‐ matting (follow‐up: 16 weeks)	Study population		RR 0.78 (0.51 to 1.20)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	351 per 1000	273 per 1000 (179 to 421)
Pain (follow‐up: 16 weeks)	Study population		RR 1.02 (0.83 to 1.24)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
	443 per 1000	442 per 1000 (359 to 537)
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; POL: polidocanol; RCT: randomised controlled trial; RR: risk ratio; SMD: standardised mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Sclerotherapy plus compression compared to sclerotherapy alone for telangiectasias and reticular veins
Patient or population: people with telangiectasias and reticular veins Setting: outpatient Intervention: sclerotherapy plus compression Comparison: sclerotherapy
Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)^*	Certainty of the evidence (GRADE)	Comments
	Risk with sclerotherapy	Risk with sclerotherapy plus compression
Resolution or improvement of telangiectasias (follow‐up: 4 ‐ 8 weeks)	‐	SMD 0.09 higher (0.19 lower to 0.37 higher)	‐	196 (2 studies)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ hyperpigmentation (follow‐up:4 ‐ 8 weeks)	Study population		RR 0.93 (0.41 to 2.07)	196 (2 studies)	⊕⊕⊕⊝ MODERATE^a	‐
	112 per 1000	104 per 1000 (46 to 232)
Adverse events ‐ matting (follow‐up: 8 weeks)	Study population		RR 1.84 (0.17 to 19.62)	96 (1 study)	⊕⊕⊝⊝ LOW^b	‐
	22 per 1000	40 per 1000 (4 to 427)
Pain	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Recurrence	See comment	‐	‐	‐	‐	The studies in this comparison did not assess this outcome
Time to resolution	See comment		‐	‐	‐	The studies in this comparison did not assess this outcome
Quality of life (follow up: 8 weeks)		SMD 0.02 lower (0.42 lower to 0.39 higher)	‐	93 (1 study)	⊕⊕⊝⊝ LOW^b
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio; SMD: standard mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

Source	Search strategy	Hits retrieved
VASCULAR REGISTER IN CRSW	1. telang* AND INREGISTER 2. Spider AND INREGISTER 3. reticular near3 vein* AND INREGISTER 4. #1 OR #2 OR #3	29.8.17 ‐ 63 21.1.19 ‐ 2 16.3.21 ‐ 82
CENTRAL via CRSW	#1 MESH DESCRIPTOR Telangiectasis EXPLODE ALL TREES 146 #2 telangiectas:TI,AB,KY 551 #3 microvaric:TI,AB,KY 1 #4 (reticular near3 vein):TI,AB,KY 27 #5 (reticular near3 varic ):TI,AB,KY 1 #6 (reticular near3 venous ):TI,AB,KY 0 #7 (thread near3 vein* ):TI,AB,KY 0 #8 (thread near3 varic* ):TI,AB,KY 1 #9 (thread near3 venous ):TI,AB,KY 0 #10 (spider near3 vein* ):TI,AB,KY 10 #11 (spider near3 varic* ):TI,AB,KY 1 #12 (spider near3 venous ):TI,AB,KY 1 #13 angioectasias:TI,AB,KY 6 #14 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 574 #15 01/01/2017 TO 22/01/2019:CD 324775 #16 #14 AND #15 177	29.8.17 ‐ 547 21.1.19 ‐ 117 16.3.21 ‐ 228
Clinicaltrials.gov	Telangiectasis OR telangiectatic OR "reticular veins" OR "reticular vein" OR "spider veins" OR "spider vein" OR "thread veins" OR "thread vein" OR angioectasias \| Interventional Studies	29.8.17 ‐ 136 21.1.19 ‐ 18 16.3.21 ‐ 30
ICTRP Search Portal	Telangiecta* OR reticular vein* OR spider vein* OR thread vein* OR angioectasias	29.8.17 ‐ 131 21.1.19 ‐ 31 16.3.21 ‐ 43
Ovid MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE 1946 to Present	1 exp Telangiectasis/ 2 telangiectas.ti,ab. 3 microvaric.ti,ab. 4 (reticular adj3 varic).ti,ab. 5 (reticular adj3 vein).ti,ab. 6 (reticular adj3 venous).ti,ab. 7 (thread adj3 vein).ti,ab. 8 (thread adj3 varic).ti,ab. 9 (thread adj3 venous).ti,ab. 10 (spider adj3 vein).ti,ab. 11 (spider adj3 varic).ti,ab. 12 (spider adj3 venous).ti,ab. 13 angioectasias.ti,ab. 14 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 15 limit 14 to yr="2017" 16 randomized controlled trial.pt. 17 controlled clinical trial.pt. 18 randomized.ab. 19 placebo.ab. 20 drug therapy.fs. 21 randomly.ab. 22 trial.ab. 23 groups.ab. 24 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 25 exp animals/ not humans.sh. 26 24 not 25 27 15 and 26	29.8.17 ‐ 45 21.1.19 ‐ 235 16.3.21 ‐ 230
Embase Ovid	1 exp Telangiectasis/ 2 telangiectas.ti,ab. 3 microvaric.ti,ab. 4 (reticular adj3 varic).ti,ab. 5 (reticular adj3 vein).ti,ab. 6 (reticular adj3 venous).ti,ab. 7 (thread adj3 vein).ti,ab. 8 (thread adj3 varic).ti,ab. 9 (thread adj3 venous).ti,ab. 10 (spider adj3 vein).ti,ab. 11 (spider adj3 varic).ti,ab. 12 (spider adj3 venous).ti,ab. 13 angioectasias.ti,ab. 14 1 or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 15 limit 14 to yr="2017" 16 randomized controlled trial/ 17 controlled clinical trial/ 18 random$.ti,ab. 19 randomization/ 20 intermethod comparison/ 21 placebo.ti,ab. 22 (compare or compared or comparison).ti. 23 ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab. 24 (open adj label).ti,ab. 25 ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab. 26 double blind procedure/ 27 parallel group$1.ti,ab. 28 (crossover or cross over).ti,ab. 29 ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. 30 (assigned or allocated).ti,ab. 31 (controlled adj7 (study or design or trial)).ti,ab. 32 (volunteer or volunteers).ti,ab. 33 trial.ti. 34 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 35 15 and 34	29.8.17 ‐ 99 21.1.19 ‐ 581 16.3.21 ‐ 487
AMED (Allied and Complementary Medicine)	1. telangiectas.ti,ab. 2. microvaric.ti,ab. 3. (reticular adj3 varic).ti,ab. 4. (reticular adj3 vein).ti,ab. 5. (reticular adj3 venous).ti,ab. 6. (thread adj3 vein).ti,ab. 7. (thread adj3 varic).ti,ab. 8. (thread adj3 venous).ti,ab. 9. (spider adj3 vein).ti,ab. 10. (spider adj3 varic).ti,ab. 11. (spider adj3 venous).ti,ab. 12. angioectasias.ti,ab. 13. or/1‐12 14. exp CLINICAL TRIALS/ 15. RANDOM ALLOCATION/ 16. DOUBLE BLIND METHOD/ 17. Clinical trial.pt. 18. (clinic* adj trial).tw. 19. ((singl or doubl* or trebl* or tripl) adj (blind or mask)).tw. 20. PLACEBOS/ 21. placebo.tw. 22. random*.tw. 23. PROSPECTIVE STUDIES/ 24. or/14‐23 25. 13 and 2	29.8.17 ‐ 0 21.1.19 ‐ 0 16.3.21 ‐ 0
CINAHL	S30 S28 AND S29 S29 EM 2017 OR EM 2018 OR 2019 EM S28 S14 AND S27 S27 S15 OR S16 OR S17 OR S18 OR S19 OR S20 OR S21 OR S22 OR S23 OR S24 OR S25 OR S26 S26 MH "Random Assignment" S25 MH "Single‐Blind Studies" or MH "Double‐Blind Studies" or MH "Triple‐Blind Studies" S24 MH "Crossover Design" S23 MH "Factorial Design" S22 MH "Placebos" S21 MH "Clinical Trials" S20 TX "multi‐centre study" OR "multi‐center study" OR "multicentre study" OR "multicenter study" OR "multi‐site study" S19 TX crossover OR "cross‐over" S18 AB placebo* S17 TX random* S16 TX trial* S15 TX "latin square" S14 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 S13 TX angioectasias S12 TX spider venous S11 TX spider varic* S10 TX spider vein* S9 TX thread venous S8 TX thread varic* S7 TX thread vein* S6 TX reticular venous S5 TX reticular varic* S4 TX reticular vein* S3 TX telangiectas* S2 (MH "Telangiectasis+") S1 TX Telangiectasis	29.8.17 ‐ 49 21.1.19 ‐ 41 16.3.21 ‐ 23

acne vulgaris	skin disease caused by overactivity of sebaceous glands
ambulatory	people treated out of the hospital setting
angiomas	dilatation or new formation of blood vessels
arterioles	small branches of an artery
atrophic blanche	small smooth ivory‐white areas on the skin with hyperpigmented borders and telangiectasias
chromophore	chemical group that absorbs light at a specific frequency
dermal	relating to skin and specially to the dermis
dorsum	the dorsal part of an organism such as human body
endothelium	tissue that forms a single layer of cells lining various organs
epidermal	non sensitive layer of the skin
erythema	superficial reddening of the skin
extravasation	escape of blood from a vessel into the tissues
fibrosis	the thickening and scarring of connective tissue
hypopigmentation	decreased pigmentation of skin area
hyperpigmentation	increased pigmentation of skin area
lipodermatosclerosis	chronic fibrosing panniculitis associated with venous insufficiency
matting	new telangiectasis after treatment
melanin	pigment responsible for determining skin and hair colours
microthrombi	small thrombus (blood clot formed in situ within the vascular system)
necrosis	death of most or all of the cells in an organ or tissue
occlusion	blockage of blood vessel
oedema	excess of watery fluid collecting in the tissue of the body and outside of blood vessels
osmotic	diffusion of fluid through a semipermeable membrane
oxyhaemoglobin	substance formed by the combination of haemoglobin with oxygen
periorbital	tissues surrounding or lining the orbit of the eye
photocoagulation	coagulation of tissue using a laser or other intense light source
photothermolysis	a method of laser skin resurfacing
polychromatic	various wavelengths or frequencies
recanalisation	process of restoring flow of the blood vessels
subcutaneous	situated or applied under the skin
subdermal	situated or lying under the skin
thermocoagulation	coagulation of tissue with high‐frequency currents
thermosclerosis	coagulation of blood vessels for heat
thrombosis	local coagulation or clotting of the blood in a part of circulatory system
vascular	relating to blood vessels
venous	relating to a vein
venules	very small veins
vesicles	small fluid‐filled bladders, sacs, or cysts

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Resolution or improvement of telangiectasias	4	613	Std. Mean Difference (IV, Random, 95% CI)	3.08 [2.68, 3.48]
1.2 Adverse events	3		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.2.1 Hyperpigmentation	3	528	Risk Ratio (M‐H, Random, 95% CI)	11.88 [4.54, 31.09]
1.2.2 Matting	3	528	Risk Ratio (M‐H, Random, 95% CI)	4.06 [1.28, 12.84]
1.3 Pain	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Resolution or improvement of telangiectasias	7	852	Std. Mean Difference (IV, Random, 95% CI)	0.01 [‐0.13, 0.14]
2.2 Adverse events	8		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.2.1 Hyperpigmentation	6	819	Risk Ratio (M‐H, Random, 95% CI)	0.94 [0.62, 1.43]
2.2.2 Matting	7	859	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.52, 1.27]
2.2.3 Bruising	4	558	Risk Ratio (M‐H, Random, 95% CI)	0.77 [0.56, 1.06]
2.2.4 Microthrombosis	4	394	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.69, 1.34]
2.2.5 Allergy	4	472	Risk Ratio (M‐H, Random, 95% CI)	0.68 [0.23, 2.01]
2.2.6 Necrosis	4	558	Risk Ratio (M‐H, Random, 95% CI)	0.07 [0.02, 0.29]
2.3 Pain	5	480	Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.44, ‐0.08]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Resolution or improvement of telangiectasias	4	473	Std. Mean Difference (IV, Random, 95% CI)	‐0.07 [‐0.25, 0.11]
3.2 Adverse events	5		Risk Ratio (IV, Random, 95% CI)	Subtotals only
3.2.1 Hyperpigmentation	4	478	Risk Ratio (IV, Random, 95% CI)	1.71 [1.10, 2.64]
3.2.2 Matting	2	323	Risk Ratio (IV, Random, 95% CI)	2.10 [1.14, 3.85]
3.2.3 Bruising	3	418	Risk Ratio (IV, Random, 95% CI)	1.62 [1.14, 2.30]
3.2.4 Microthrombosis	1	129	Risk Ratio (IV, Random, 95% CI)	1.04 [0.78, 1.39]
3.2.5 Allergy	3	452	Risk Ratio (IV, Random, 95% CI)	1.38 [1.01, 1.88]
3.2.6 Necrosis	2	392	Risk Ratio (IV, Random, 95% CI)	16.31 [3.14, 84.79]
3.3 Pain	4	409	Risk Ratio (M‐H, Random, 95% CI)	1.49 [0.99, 2.25]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Resolution or improvement of telangiectasias	3	348	Std. Mean Difference (IV, Random, 95% CI)	0.01 [‐0.20, 0.22]
4.2 Adverse events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
4.2.1 Hyperpigmentation	2	288	Risk Ratio (M‐H, Random, 95% CI)	0.74 [0.59, 0.93]
4.2.2 Matting	2	288	Risk Ratio (M‐H, Random, 95% CI)	0.89 [0.58, 1.36]
4.3 Pain	3	348	Std. Mean Difference (IV, Random, 95% CI)	6.22 [5.70, 6.73]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Resolution or improvement of telangiectasias	2	125	Std. Mean Difference (IV, Random, 95% CI)	0.45 [‐0.11, 1.02]
5.2 Adverse events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
5.2.1 Hyperpigmentation	2	125	Risk Ratio (M‐H, Random, 95% CI)	0.49 [0.09, 2.50]
5.2.2 Matting	1	99	Risk Ratio (M‐H, Random, 95% CI)	0.31 [0.01, 7.53]
5.2.3 Bruising	1	26	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.02, 1.00]
5.2.4 Microthrombosis	1	99	Risk Ratio (M‐H, Random, 95% CI)	1.32 [0.45, 3.87]
5.3 Pain	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Resolution or improvement of telangiectasias	2	187	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.26, 0.34]
6.2 Adverse events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
6.2.1 Hyperpigmentation	2	187	Risk Ratio (M‐H, Random, 95% CI)	2.12 [0.44, 10.23]
6.2.2 Matting	2	187	Risk Ratio (M‐H, Random, 95% CI)	6.12 [1.04, 35.98]
6.2.3 Bruising	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.60 [0.35, 1.04]
6.2.4 Microthrombosis	2	187	Risk Ratio (M‐H, Random, 95% CI)	1.39 [0.70, 2.76]
6.3 Pain	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Resolution or improvement of telangiectasias	5	593	Std. Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.25, 0.07]
7.2 Adverse events	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
7.2.1 Hyperpigmentation	4	262	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.40, 0.80]
7.2.2 Matting	2	162	Risk Ratio (M‐H, Random, 95% CI)	1.00 [0.46, 2.19]
7.2.3 Bruising	1	40	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.60, 1.04]
7.2.4 Necrosis	3	202	Risk Ratio (M‐H, Random, 95% CI)	1.60 [0.20, 12.74]
7.3 Pain	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Resolution or improvement of telangiectasias	2	710	Std. Mean Difference (IV, Random, 95% CI)	5.68 [5.14, 6.23]
8.2 Adverse events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
8.2.1 Hyperpigmentation	2	656	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.35, 1.99]
8.2.2 Matting	2	656	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.21, 3.28]
8.3 Pain	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Resolution or improvement of telangiectasias	2	191	Std. Mean Difference (IV, Random, 95% CI)	0.79 [0.50, 1.09]
9.2 Adverse events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
9.2.1 Hyperpigmentation	2	191	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.62, 1.01]
9.2.2 Matting	2	191	Risk Ratio (M‐H, Random, 95% CI)	0.78 [0.51, 1.20]
9.3 Pain	2	191	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.83, 1.24]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
10.1 Resolution or improvement of telangiectasias	2	196	Std. Mean Difference (IV, Random, 95% CI)	0.09 [‐0.19, 0.37]
10.2 Adverse events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
10.2.1 Hyperpigmentation	2	196	Risk Ratio (M‐H, Random, 95% CI)	0.93 [0.41, 2.07]
10.2.2 Matting	1	96	Risk Ratio (M‐H, Random, 95% CI)	1.84 [0.17, 19.62]
10.3 Quality of life	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

*Study characteristics*
Methods	Study design: a double‐blind, controlled clinical trial study Method of randomisation: "Regions were randomly assigned one or other procedure as follows; the right limb (if both legs were involved) or the upper region (if only one leg was involved) were always treated first. The assignment of the first region to be treated to liquid or foam was performed according to a list of 38 random numbers from 0 to 75 created by an specific software. Each patient had an identification number according strict chronological recruitment order, if this number was in the list of random numbers then the patient received first foam and if not received liquid sclerosant first." Blinding: participant ‐ yes; treating doctor ‐ no; outcome assessors ‐ yes Power calculation: no details provided Total number of participants: 75 people with reticular or postoperative varices were enrolled and sclerotherapy was performed with liquid and with foam (Tessari method) using the same quantity of sclerosant for homogeneous varicose regions, to a total of 150 procedures Total number of procedures: 150 (sclerotherapy with liquid polidocanol and sclerotherapy with foam of polidocanol) Treatment localisation: lower limbs Number of exclusions post‐randomisation: none Number of withdrawals and reasons: 4 had left the study by the 90‐day follow‐up interval and 12 by the 365‐day assessment
Participants	Setting: outpatient site Country: Spain Gender: 6 men and 69 women Age: mean 59 years (range: 23 – 78) Inclusion criteria: people with primary reticular varices (those of more than 2 mm of diameter) or postoperative varices in more than one region that did not involve the saphenofemoral junction Exclusion criteria: patients with truncal varices with junctional (terminal valve) and extra‐junctional incompetence, postoperative varices that involved the saphenofemoral junction, post‐thrombotic varices with occluded deep veins, varices secondary to arteriovenous fistulas, bilateral varices of asymmetric calibre, unilateral varices with asymmetric calibre between regions, chronic ischaemia of the lower limbs, severe arterial hypertension (blood pressure > 180/95 mmHg), and those being treated with anticoagulants and anti‐inflammatories and/or diuretics for other pathologies, to avoid these affecting the appearance or degree of possible secondary effects
Interventions	Technique: all participants underwent 1 session of sclerotherapy in which both sclerosants (foam and liquid polidocanol) were given. Participants received the sclerotherapy in both regions by the same doctor, whether in different limbs or the same limb in different regions Treatment 1: 2 mL injection of foam into only 1 varicose vein. The concentration depended on the diameter of the vein measured with Duplex ultrasound with the participant standing. Foam was obtained from 0.5 mL of liquid polidocanol mixed with air at a ratio of 1:4, using the Tessari method which uses a 3‐way stopcock to mix the sclerosant. So 2 mL of foam contained 0.5 mL of polidocanol. After the sclerosant was injected, the sclerosed vein was compressed for 48 h with stockings at a pressure of 25 – 35 mmHg, while participants resumed a normal life style and regularly applied heparinoid ointment (3 times a day) Treatment 2: 0.5 mL liquid polidocanol injection in only one varicose vein in the corresponding region. An antegrade injection technique was used with the same kind of material (a 2 mL syringe and a 25 G, 5/8 needle) and the same postoperative care with compression and heparinoid as the study group. The same quantity of sclerosant was used in each injection in the foam and liquid sclerosant groups Duration of follow‐up: 365 days Use of compression: stockings 25 ‐ 35 mmHg
Outcomes	Efficacy: assessed according to whether sclerosis of the vein was complete, as shown by duplex ultrasound. Sclerosis was considered complete when the lumen of the vein was sealed and the vein occluded. Total efficacy corresponded to complete sclerosis and partial efficacy to incomplete sclerosis when obliteration of the lumen was less than 100% The length of the sclerosed vein, measured in cm with a tape measure Side effects: pain in the treated region graded on an ordinal scale (absent, mild, moderate, or severe); requirement for analgesic treatment and type of analgesic given; inflammation in the treated region and degree of severity of inflammation (mild, moderate, severe) according to clinical criteria; appearance of skin pigmentation in the sclerosis region; formation of bulla, cutaneous necrosis and other effects Efficacy was assessed at 15, 30, and 90 days after the sclerotherapy and safety was evaluated at 15, 30, 90, and 365 days
Funding sources	No details provided
Declarations of interest	No details provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "The assignment of the first region to be treated to liquid or foam was performed according to a list of 38 random numbers from 0 to 75 created by an specific software. Each patient had an identification number according strict chronological recruitment order, if this number was in the list of random numbers then the patient received first foam and if not received liquid sclerosant first."
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both the participant and the research assistant who assessed the clinical and ultrasound results were blind to the type of treatment applied in each area. The doctor who performed the treatment was not blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Clinical and ultrasound results were assessed by a member of the research team other than the doctor who had performed the treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Of the 75 original participants, four had left the study by the 90‐day follow‐up interval and 12 by the 365‐day assessment
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: a randomised, controlled clinical trial study Method of randomisation: participants were allocated to 1 of the 2 study subgroups by selection of a sealed envelope Blinding: participant ‐ no; treating doctor ‐ no; outcome assessors ‐ yes Power calculation: no details provided Total number of participants: 50 people with telangiectasias or reticular veins, 100 legs for procedure Total number of procedures: 100 (sclerotherapy with polidocanol and compression stocking) Treatment localisation: lower limbs Number of exclusions post‐randomisation: none Number of withdrawals and reasons: none
Participants	Setting: outpatient site Country: Germany Gender: 4 men and 46 women Age: not mentioned Inclusion criteria: people with telangiectasias or reticular varices Exclusion criteria: pregnancy, classification CEAP higher than stage C2, allergy to sclerosing agent, walking range < 200 m
Interventions	Sclerotherapy with polidocanol. Group A received sclerotherapy only, i.e. eccentric compression using low‐stretch bandages over rolled gauze for 24 hrs Group B received an additional week of concentric stockings of 18 to 20 mmHg above the ankle
Outcomes	Improvement or resolution of telangiectasias or reticular veins Adverse events: pain, itching, burning Hyperpigmentation
Funding sources	No details provided
Declarations of interest	None declared
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Sealed envelope
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding of participants
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blinding of 2 experts to analyse the photography after procedure
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No details given
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: multicentre, split‐body, randomised comparative trial (a pilot study) Method of randomisation: drawing of lots Blinding: participant ‐ no, treating doctor ‐ no Power calculation: no Total number of participants randomised: 24 Total number of participants analysed: 20 Total number of procedures: 40 Treatment localisation: lower limbs Number of exclusions post‐randomisation: 4 (information obtained through personal correspondence with Jean‐Patrick Benigni, MD) Number of withdrawals and reasons: none
Participants	Setting: 4 outpatient centres (information obtained through personal correspondence with Jean‐Patrick Benigni, MD) Country: France Gender: women Age: mean 37.7 (range 18 ‐ 65) Inclusion criteria: "clear photo type" (classifications I to III on the Fitzpatrick classification scale), "roughly symmetrical reticular veins and telangiectases of the lateral thigh surface", reflux of reticular varices of at least 1 point on continuous Doppler Exclusion criteria: incompetence of the large saphenous veins or their collaterals, incompetence of the deep veins, perineal varices, skin condition of the lateral face of the thigh, obesity (BMI > 30), pregnancy, psychiatric trouble, a contraindication to sclerotherapy, hormonal treatment within 6 months of enrolment
Interventions	Treatment 1: 1 thigh was treated with polidocanol foam 0.25% by the Monfreux method Treatment 2: the other thigh was treated with polidocanol solution 0.25% Duration of follow‐up: 5 sessions every 15 ± 2 days, and a control visit 15 days after the last session
Outcomes	Efficacy: appearance of telangiectasias on visual analogue scales (0 to 10) as assessed by the treating doctors (days 0, 15, 30, 45, 60 & 75) and by participants (days 0 and 75). 4 criteria were assessed: colour, density, relief and surface Adverse effects: as assessed by the treating physician: ecchymosis, thrombi, microthrombi, matting, pigmentation, necrosis Number of points of injection The quantity of sclerosant injected
Funding sources	No details provided
Declarations of interest	No details provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Drawing of lots
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding is not mentioned for participants or treating doctors. Foam and liquid sclerosants have distinct appearances on injection
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details given
Incomplete outcome data (attrition bias) All outcomes	High risk	4 people were "lost of view" as per personal communication with Dr. Benigni. No explanation was provided in the published article
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

PERMALINK

Treatment for telangiectasias and reticular veins

Luis CU Nakano

Daniel G Cacione

Jose CC Baptista-Silva

Ronald LG Flumignan

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Sclerotherapy compared to placebo for treatment of telangiectasias and reticular veins.

Summary of findings 2. Sclerotherapy (polidocanol) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins.

Summary of findings 3. Sclerotherapy (STS) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins.

Summary of findings 4. Sclerotherapy (hypertonic saline) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins.

Summary of findings 5. Sclerotherapy (chromated glycerin) compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins.

Summary of findings 6. Foam compared to sclerotherapy (any sclerosant) for treatment of telangiectasias and reticular veins.

Summary of findings 7. Laser compared to sclerotherapy for treatment of telangiectasias and reticular veins.

Summary of findings 8. Laser plus sclerotherapy compared to sclerotherapy for treatment of telangiectasias and reticular veins.

Summary of findings 9. Sclerotherapy (hypertonic glucose plus polidocanol) compared to sclerotherapy (hypertonic glucose).

Summary of findings 10. Sclerotherapy plus compression compared to sclerotherapy alone for telangiectasias and reticular veins.

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Type of study

Setting

Unit of analysis

Study participants

Interventions

Outcomes

Excluded studies

Ongoing studies

Risk of bias in included studies

2.

3.

Allocation

Random sequence generation

Allocation concealment

Blinding

Blinding of participants and personnel

Blinding of outcome assessment

Incomplete outcome data

Selective reporting

*Study characteristics*
Methods	Study design: prospective, randomised, triple‐blind, controlled, parallel‐group clinical trial Method of randomisation: "Participants were randomly assigned using an open‐source, web‐based randomisation software (Stat Trek, http://stattrek.com/statistics/random‐number‐generator.aspx) to 1 of 2 treatment groups: group 1 to receive 0.2% polidocanol diluted in 70% hypertonic glucose; group 2 to receive 75% hypertonic glucose. The computer generated allocation sequence was kept by an independent nurse, who prepared opaque, sealed envelopes for each group. The nurse prepared the medications in a room separate from the treatment room." Blinding: participant ‐ yes; treating doctor ‐ yes; outcome assessors ‐ yes Power calculation: yes Total number of participants: 93 Total number of procedures: 93 Treatment localisation: lower limbs Number of exclusions post‐randomisation: none Number of withdrawals and reasons: none
Participants	Setting: outpatient site Country: Brazil Gender: women. "The study population consisted of a calculated sample of adult women consecutively recruited among patients seeking treatment at the specialized out patient clinic of our institution" Age: range 24 ‐ 62 Inclusion criteria; eligible participants were all women aged 18 to 69 years who had at least 1 reticular vein with a minimum length of 10 cm in 1 of their lower limbs with mild venous disease classified as CEAP C1, and all were available to attend the appointments Exclusion criteria: venous disease with a CEAP clinical class other than C1, pregnancy or puerperium, allergy to polidocanol or glucose, restricted mobility, PAD, diabetes mellitus, uncontrolled systemic disorders, dermatitis at the treatment site, asthma, migraine, previous DVT, family history of DVT, acute thrombophlebitis, known thrombophilia or any hypercoagulable state, and use of anticoagulants. Patients who failed to attend the treatment session or the follow‐up visits were also excluded
Interventions	Treatment 1: 0.2% polidocanol diluted in 70% hypertonic glucose Treatment 2: 75% hypertonic glucose The treatment area on the participant’s lower limb was defined as a rectangle of approximately 600 cm² (25 cm long × 15 cm wide) on the lateral aspect of the distal midthigh and the proximal and middle leg of 1 of the limbs. The lower limbs were photographed before and after treatment using a high‐definition digital camera All sclerotherapy procedures were performed by the same physician. Both medications were in liquid form and identical in appearance within the syringes (colourless, odourless, and with similar viscosity). The maximum volume per puncture was 0.3 mL, and punctures were performed until whitening of the reticular veins occurred in the treatment area. After the procedure, elastic compression bandages (Atadress; Adamed) were applied directly over the treated area for 24 hours Duration of follow‐up: 60 days Use of compression: elastic compression bandage
Outcomes	The primary efficacy end point was complete elimination of the reticular veins by 60 days after sclerotherapy treatment with the study medications. To assess this outcome, the reticular veins were measured on images obtained before treatment (day 0) and after treatment (day 60) using ImageJ software. The linear measurements of reticular veins before treatment and residual veins after treatment were captured in pixels, which were then converted to millimetres. Each image was analysed by 2 independent observers who were blinded to the medication used. The safety outcomes were analysed at each post‐treatment visit for the occurrence of serious adverse events (chest pain, transient neurological abnormalities, anaphylaxis, accidental arterial puncture, tissue necrosis, DVT, and PE), minor adverse events (scars, cough, superficial thrombophlebitis, telangiectatic matting, allergies, lipothymia, and scotomas), and particularly pigmentation running the course of the treated veins, which was analysed based on direct measurements performed on post‐treatment images using ImageJ software Secondary outcomes: skin colour, number of punctures, volume of medication used, occurrence of haematomas, residual veins in relation to pigmentation, comparison of current pain with pain at the time of previous treatments, treatment‐related cough, migraine, oedema, early (day 7) and late (day 60) phlebitis, telangiectatic matting, and lipothymia
Funding sources	No details provided
Declarations of interest	None declared
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Participants randomly assigned in a 1:1 ratio using open‐source, web‐based randomisation software (Stat Trek, http://stattrek.com/statistics/random‐number‐generator.aspx)
Allocation concealment (selection bias)	Low risk	Quote: "The computer generated allocation sequence was kept by an independent nurse,who prepared opaque, sealed envelopes for each group. The nurse prepared the medications in a room separate from the treatment room."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Both medications were in liquid form and identical in appearance within the syringes (colourless, odourless, and with similar viscosity)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Each image was analysed by 2 independent observers who were blinded to the medication used. Still blindly, the safety outcomes were analysed at each post treatment visit for the occurrence of serious adverse events."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Of 106 eligible participants, 51 were randomised to receive 0.2% polidocanol diluted in 70% hypertonic glucose; in this group 1 did not receive allocated intervention and 7 lost to follow‐up; and 55 to receive 75% hypertonic glucose alone, in this group 1 did not receive allocated intervention and 4 lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: a double‐blind, double‐paired comparison, placebo‐controlled study Method of randomisation: not mentioned Blinding: participant ‐ yes, treating doctor ‐ yes Power calculation: not mentioned Total number of participants: 20 Total number of procedures: 80 Treatment localisation: 4 quadrants of legs on each participant Number of exclusions post‐randomisation: none Number of withdrawals and reasons: not mentioned
Participants	Setting: outpatient site Country: USA Gender: women Age: range 29 ‐ 55 Inclusion criteria: bilaterally symmetrical telangiectasias of the lower extremities Exclusion criteria: women taking hormonal therapy, anticoagulants or disulfiram
Interventions	Technique: each participant's legs were divided into 4 quadrants Treatment 1. sodium tetradecyl sulfate (STS) 0.5% Treatment 2. polidocanol 0.5% Treatment 3. heparsal (saline 20% with heparin 100 units/mL) Control: placebo ‐ normal saline 0.9% Duration of follow‐up: 24 weeks Use of compression: no details provided
Outcomes	Visual improvement: clinical assessment of improvement: scale of 1 to 5 (poor, fair, moderate, good, excellent) Adverse events: hyperpigmentation: scale of 1 to 3 (mild, moderate, severe); itching: scale of 1 to 4 (none, mild, moderate, severe); neovascularization: scale of 1 to 3 (mild, moderate, severe) Participant satisfaction (dissatisfied, neither, satisfied, very satisfied) Pain: scale of 1 to 4 (none, mild, moderate, severe) Number of treatments required for clearance (from 1 to > 6)
Funding sources	No details provided
Declarations of interest	No details provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details given
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participaents and doctor were blinded for sclerosant agent
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details given
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	High risk	Some of the adverse reactions were not statistically analysed by sclerosing agent used. Patient satisfaction data were not separated based on sclerosing agent used
Other bias	High risk	Participants received separate simultaneous treatments and analysis, and thereby the risks of bias by carry‐over effect exist

*Study characteristics*
Methods	Study design: randomised, paired study Method of randomisation: not mentioned Blinding: participant ‐ yes, treating doctor ‐ no, outcomes assessors ‐ yes Power calculation: not mentioned Total number of participants: 14 Total number of procedures: 28 Treatment localisation: 28 vessel pairs were treated; 13 blue and 15 red vessels; the vessels were divided into 4 groups according to size; 0.3 mm, 0.3 ‐ 0.5 mm, 0.5 ‐ 1 mm, and 1 ‐ 2.5 mm Total vessel treated: 28 vessel pairs were treated, 13 blue and 15 red vessels. Participants with skin types ranging from I to V. The vessels were divided into 4 groups according to size: 0.3 mm, 0.3 – 0.5 mm, 0.5 – 1 mm, and 1 – 2.5 mm Number of exclusions post‐randomisation: none Number of withdrawals and reasons: none
Participants	Setting: outpatient site Country: Denmark Gender: women Age: mean: 36.8, SD: 9.3, range: 25 – 60 years Inclusion criteria: only participants having a pair of close‐to‐identical telangiectasias with identical diameters (less than 2.5 mm) located on lower extremities and with the same colour were included in the study In each group, specific parameters for pulse duration and fluence were selected according to the vessel colour and diameter Exclusion criteria: "participants with more than moderately suntanned skin or participants who had been exposed to sunlight within one week prior to the date of treatment were excluded from the study. Pre‐cancers or with ski malignancies and with Koebner phenomena or light, sensitive skin diseases were excluded."
Interventions	Treatment 1: manually‐adjusted laser fluences, guided by clinical endpoints of visual coagulation Treatment 2: theoretically optimised and clinically verified fixed fluence settings Technique: 1 of the paired vessels was randomly chosen and treated with a theoretically optimised and clinically verified. These settings were used as the starting point when treating the corresponding vessel on the other side, but in this case the laser fluence was manually adjusted to the lowest level that could produce a visual coagulation or visual obstruction of the blood flow (the clinically judged fluence) 1 or 2 treatment sessions were performed with a single pass. Prior to treatment, a thin layer of transparent optical index‐matching gel was applied to the skin surface Duration of follow up: 4 months Use of compression: not mentioned
Outcomes	Pain associated with treatment ‐ the participants were asked to rate the pain according to a VAS (0 – 10) Degree of erythema and oedema ‐ the clinical investigator registered the degree of erythema and oedema based on 3 categories: 0 none, 1 medium, and 2 heavy at 5 min post‐treatment The first follow‐up took place 2 months after the first treatment and a second treatment was then performed if necessary. The second follow‐up visit took place 4 months after the first treatment
Funding sources	No details provided
Declarations of interest	None declared
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	States "randomised", no further details given
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No details given
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The vessel clearances were evaluated, using close‐up photographs taken prior to the first treatment and at the 2‐month and 4‐month follow‐up visits, by both the clinical investigator and the participants
Incomplete outcome data (attrition bias) All outcomes	Low risk	None absent
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: double‐blinded, randomised study Method of randomisation: coin toss (information obtained through study author Mitchell P Goldman, MD) Blinding: participant ‐ yes; treating doctor ‐ yes; outcome assessors ‐ yes Power calculation: not mentioned Total number of participants: 129 Total number of procedures: 129 Treatment localisation: leg veins Categories by size of veins: < 1 mm in diameter = 42 patients; 1 ‐ 3 mm = 41 participants and 3 ‐ 6 mm = 46 participants Number of exclusions post‐randomisation: none Number of withdrawals and reasons: not mentioned
Participants	Setting: outpatient site Country: USA Gender: not mentioned Age: not mentioned Inclusion criteria: varicose, reticular and/or telangiectatic leg veins Exclusion criteria: incompetence at the saphenofemoral or saphenopopliteal junctions
Interventions	Treatment 1. Vein less than 1 mm in diameter were randomised to be treated with either polidocanol 0.5% or STS 0.25% Treatment 2. Veins 1 ‐ 3 mm in diameter with polidocanol 1% or STS 0.5% Treatment 3. Veins 3 ‐ 6 mm in diameter to polidocanol 3% or STS 1.5% Treatment was performed in a standard technique Photographs were taken and questionnaires were administered before treatment and at 1, 4 and 16 weeks after treatment Duration of follow‐up: 16 weeks Use of compression: not mentioned
Outcomes	Efficacy: 3 vascular surgeons blinded to intervention agent assessed photographs from baseline, week 1, week 4, and week 16 on a scale of 1 to 5 Adverse sequelae: data were not separated for veins < 1 mm Participant satisfaction: data were not separated for veins < 1 mm
Funding sources	Kreussler & Co GmbH (manufacturer of sclerosant), Beisdorf‐Jobst (manufacturer of compression hosiery)
Declarations of interest	None declared
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Coin toss (information provided by study author)
Allocation concealment (selection bias)	Low risk	Physician was given the solution to inject by nurse (information provided by study author)
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The treating physician was blinded as to the agent being injected
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Blind assessment by 3 vascular surgeons
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	No details given
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: multicentre, prospective controlled randomised trial Method of randomisation: not mentioned Blinding: participant ‐ no; treating doctor ‐ no; outcome assessors ‐ not reported Power calculation: not mentioned Total number of participants: 105 Total number of procedures: 199 Treatment localisation: leg veins Number of exclusions post‐randomisation: none Number of withdrawals and reasons: not mentioned
Participants	Setting: outpatient site Country: France Gender: male and female Age: range 20 ‐ 82 years Inclusion criteria: varicose, reticular or telangiectatic leg veins or both, documented thrombophilia Exclusion criteria: mental or psychiatric disturbance, pregnancy, renal failure, uncontrolled arterial hypertension, coagulopathy
Interventions	Treatment 1: warfarin plus sclerotherapy Treatment 2: nadroparin plus sclerotherapy
Outcomes	Occurrence of a symptomatic or asymptomatic DVT or PE
Funding sources	No details provided
Declarations of interest	No details provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not reported in the study
Allocation concealment (selection bias)	Unclear risk	Not reported in the study
Blinding of participants and personnel (performance bias) All outcomes	High risk	Impossible to blind participants due to interventions
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Not reported in the study
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Not reported in the study
Selective reporting (reporting bias)	Unclear risk	Not reported in the study
Other bias	Unclear risk	Not reported in the study

*Study characteristics*
Methods	Study design: single‐centre, split‐body, randomised comparative trial comparing hypertonic 20% saline + 2% lignocaine 2% versus POL 0.5% versus long‐pulsed neodymium‐yttrium aluminium garnet (Nd:YAG) Method of randomisation: no details provided Blinding: participant ‐ no, treating doctor ‐ no Power calculation: no Total number of participants randomised: 285 Total number of participants analysed: 244 Total number of procedures: 288 Treatment localisation: lower limb Number of exclusions post‐randomisation: no details provided Number of withdrawals and reasons: 41 lost to follow‐up
Participants	Setting: outpatient site Country: Romania Gender: women Age: mean 37.7 (range 18 ‐ 65) Inclusion criteria: "patients over 18 with primary leg telangiectasias up to 2 mm in diameter (C1A) as single objective sign and those that accepted to enter the study signed the informed consent form." Exclusion criteria: ".. i) Patients with symptoms associated with telangiectasias (C1S); ii) patients with superficial venous reflux assessed with Doppler ultrasound of the lower limbs; iii) patients with deep venous thrombosis or post‐thrombotic syndrome (ES); iv) pregnant or breastfeeding patients; and v) patients with neoplasms or other systemic conditions or under chronic treatment for any other disease."
Interventions	Treatment 1: HS group ‐ treated with hypertonic: 20% saline/2% lignocaine Treatment 2: POL group with polidocanol: 0.5% Treatment 3: LAS group with Nd:YAG laser with a wavelength of 1064 nm Duration of follow‐up: "There were two identical sessions at 60‐day interval. Assessment of vessel clearing and complications was conducted at 60 and 120 days." Use of compression: not reported
Outcomes	Efficacy: 6‐point scale: 0: no change; 1: 1% ‐ 20% cleared; 2: 21% ‐ 40% cleared; 3: 41% ‐ 60% cleared; 4: 61% ‐ 80% cleared; and 5: 81% ‐ 100% cleared Adverse effects: burns, hypo‐ and hyperpigmentation, and thrombosis
Funding sources	No funding received
Declarations of interest	None declared
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	States "randomised" but no other details given
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	High risk	Blinding was not possible due to different techniques
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details given
Incomplete outcome data (attrition bias) All outcomes	Low risk	41/285 participants lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: A single‐blind, randomised, comparative study Method of randomisation: this study was a randomised, single‐blinded trial. Area treated and type of veins: only the lateral face of the thigh was considered for the study. A single leg per person was treated. If both thighs were affected, only the left one was treated and evaluated for the study, as defined by the study protocol. Each participant was randomly assigned either to chromated glycerin, POL solution, or POL foam Blinding: participants were unaware of the choice of the sclerosing method. The treating physician (P.K.) was not blinded. A doubled‐blinded study is not realizable with the different sclerosing aware of the sclerosing agent used, because of the great difference in viscosity between glycerin and POL Power calculation: not mentioned Total number of participants: 150 Total number of procedures: 150 Treatment localisation: lateral face of the thigh Number of exclusions post‐randomisation: none Number of withdrawals and reasons: 3 lost to follow‐up
Participants	Setting: outpatient site Country: Switzerland Gender: women Age: range 17 ‐ 80 years, mean: 46.5. Inclusion criteria: consecutive, informed, consenting women who were presenting with primary telangiectasias and reticular leg veins on the lateral face of the thigh (C1 A or S) Exclusion criteria: reflux in the deep veins, saphenous trunk, saphenous junctions or saphenous collateral, incompetent perforators, non‐compressible deep or superficial veins, recanalised thrombus, allergy against chrome or polidocanol, and previous sclerotherapy
Interventions	Treatment 1: chromated glycerin Treatment 2: POL solution Treatment 3: POL foam Technique: 2 mL syringes were used for chromated glycerin and POL solution, whereas 2‐mL sterilised glass syringes were used for the foam technique. Injections were performed with a 30.5‐gauge needle. All treatments were performed with the participant in the supine position. Approximately 60 to 100 injections were performed during the session. Reticular feedings veins were injected before the telangiectasias. Participants remained supine for 5 minutes after the last injection before a compressive bandage was applied with either an elastic band or a graduated compressive stocking (26 ‐ 33 mm Hg), which was worn for 1 week during the day Number of sessions: A single sclerosing session was performed in each participant. Treatment sites were photographed immediately before and after the treatment in supine position. Immediately after the treatment, the participants were asked to assess the pain score on a visual scale Duration of follow up: 5 weeks Use of compression: graduated compressive stocking
Outcomes	Visual improvement: participants were questioned about their satisfaction using a visual scale ranging from negative results to great satisfaction. The physician had the possibility of assessing satisfaction on a scale from 0 to 100, with 100 representing the maximal satisfaction rate. A control photograph was performed at 5 weeks after treatment in similar conditions as those set for the pretreatment picture. Two independent experts who were not involved in the treatment phase and who were blinded to the sclerosant used were asked to analyse the photographs and to give an efficacy score or a vessel clearance score from 0 to 10 and to report side effects. To assess the intra‐observer reproducibility of photograph analysis, the expert, still blinded, made a second analysis of the same pictures 1 month later Side effects: the treating physician, not blinded to the agent, checked for immediate side effects or those reported by the participants. He also identified microthrombi, pigmentations or matting, which may be difficult to evaluate on the photographs
Funding sources	No details provided
Declarations of interest	No details provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	States "randomised", no further details given
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	High risk	The treating physician, not blinded to the agent
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Two independent experts who were not involved in the treatment phase and who were blinded to the sclerosant used were asked to analyse the photographs and to give an efficacy score or a vessel clearance score from 0 to 10 and to report side effects. Both experts are phlebologist physicians skilled with sclerotherapy. To assess the intraobserver reproducibility of photograph analysis, the expert, still blinded, made a second analysis of the same pictures 1 month later
Incomplete outcome data (attrition bias) All outcomes	Low risk	Only 3 participants lost to follow‐up
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: prospective randomised double‐blind trial Method of randomisation: computer‐generated random table Blinding: participants ‐ yes, doctor ‐ yes, outcome assessor ‐ yes Power calculation: calculations showed that 100 participants, 50 in each group, were required to detect a true difference of half a SD at a 1‐sided 5% significance level with a power of 80% Total number of patients: 110 Total number of procedures: 110 Treatment localisation: lateral thigh Number of exclusions post‐randomisation: none Number of withdrawals and reasons: 8 participants; 5 lost to follow‐up and 3 for poor quality of the accompanying photos
Participants	Setting: outpatient site Country: Switzerland Gender: women Age: not mentioned Inclusion criteria: women were eligible if presenting for cosmetic reasons for first‐time sclerotherapy of lateral thigh reticular or telangiectatic veins (C1A or S). Participants had no evidence of superficial or deep vein insufficiency as assessed by duplex ultrasound Exclusion criteria: allergy to chrome No patient declined participation, and no patient reported chrome allergy, so no patient was excluded from the study
Interventions	Treatment 1: pure chromated glycerin (glycerin 72% and chromium alum 0.8%, Scleremo, Laboratoires Bailleul, Paris, France) Treatment 2: chromated glycerin mixed with ⅓ lidocaine‐epinephrine 1% The same physician treated all included participants. The whole treated thigh area was photographed immediately before sclerotherapy in a supine position to avoid arbitrary selection of a limited skin surface. The same digital camera (Coolpix 990, Nikon), lighting conditions (flash), and focal distance were used. Injections were performed using 2‐mL silicone syringes and a 30G 0.5‐in. needle with the participant in a supine position. The maximum amount of injected sclerosing solution was 10 mL per participant. 60 to 80 injections of very small volumes of sclerosing agent were given during treatment session. Reticular feeding veins were injected before telangiectasias. Telangiectasias were treated one after the other without re‐injecting the same area. Immediately after treatment, participants were asked to score their pain using a visual 100‐point scales (0 = no pain, 100 = maximum pain). Participants remained supine for 5 minutes after their last injection. Subsequently, a thigh‐length compression stocking (23 – 32 mmHg) was applied Duration of follow‐up: 3 weeks Use of compression: compression stocking
Outcomes	Participant pain scores (participants graded their pain by drawing a line on the scale) Rate of clinical vessel disappearance
Funding sources	No details provided
Declarations of interest	None declared
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Before treatment, each participant was randomly assigned (computer‐generated random table) to pure chromated glycerin (glycerin 72% and chromium alum 0.8%, Scleremo, Laboratoires Bailleul, Paris, France) or to CGX
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and the treating physician were blinded to the treating agent. To maintain double‐blind conditions, a dedicated non‐blinded nurse prepared syringes for injection after randomisation in an adjacent room. The visual aspect of syringes and viscosity were similar
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Two independent blinded experts with extensive sclerotherapy experience analysed the photographs using a visual a priori score of vessel disappearance
Incomplete outcome data (attrition bias) All outcomes	Low risk	8 participants; 5 lost to follow‐up and 3 for accompanying photos of poor quality
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: randomised, controlled pilot study Method of randomisation: randomisation list with software PASS 2008 Blinding: participants ‐ no, doctor ‐ no, outcome assessors ‐ yes Power calculation: not mentioned Total number of patients: 15 Total number of procedures: 30 Treatment localisation: leg veins Number of exclusions post‐randomisation: none Number of withdrawals and reasons: 1 lost at last visit
Participants	Setting: outpatient site Country: Germany Gender: women Age: range 28 ‐ 62 years (mean: 44 years) Inclusion criteria: written informed consent, White ethnicity, and Fitzpatrick skin type I–IV Exclusion criteria: age younger than 18 years, pregnancy, breast‐feeding, suntan, and a risk of non‐compliance 5 out of 15 women were post‐menopausal, and the others used contraception. Before laser therapy was applied, underlying chronic venous insufficiency was excluded by duplex ultrasonography. The vessel diameter was measured by means of a dermatoscope with an integrated scale
Interventions	Groups: "Patients were assigned to Groups A, B, or C. For the first five patients (Group A), we used a mean radiant exposure of 64.07 J/cm2, a mean pulse duration of 26.65 ms, and a spot size of 4 mm. Because we neither observed any side effects nor any visible response, the radiant exposure was increased. For the next five patients (Group B), we applied mean radiant exposures of 96 J/cm2 and mean pulse durations of 54.8 ms with the 4 and 6 mm handpiece. After 6 weeks, slight vessel clearance was seen without any adverse events so that we further increased the radiant exposure. For the last five patients (Group C), we applied mean radiant exposures of 107 J/cm2, mean pulse durations of 85.8 ms, and a spot size of 6 mm as well as double pulses for the last two patients." Technique: "All patients had similarly sized telangiectatic leg veins on both legs and were randomly allocated to either PDL therapy (Sclerolaser plusTM, Candela Corp., Wayland, MA) or diode laser therapy (MeDioStar, Asclepion, Jena, Germany) on either leg. The treatment allocation was deposited in a closed envelope. The envelopes were numbered consecutively from 1 to 15, and the investigator always opened the envelope with the lowest available parameters: Wavelength 595 nm, radiant exposure 16 J/cm2, elliptical spot of 2 7 mm, and pulse duration 1.5 ms. The PDL had an integrated cryogen spray cooling system. Before the application of ICG, 11 patients received test spots with the diode laser alone (808 nm, spot size 4 or 6 mm, radiant exposure 75–110 J/cm2, pulse duration 26–87 ms) for safety reasons. The same laser parameters were applied for diode alone and ICG þ DL besides the application of double pulses. Afterwards, patients obtained an intravenous access in the median cubital vein. ICG (Pulsion Medical Systems AG, Munich, Germany) was dissolved in an aqueous solvent (50 mg of ICG in 10 mL of solvent) at a concentration of 5 mg/mL and immediately intravenously injected as a bolus. The administered ICG‐concentration was 2 mg/kg body weight ICG fluorescence was visualized with a commercial fluorescence imaging system (IC‐View1; Pulsion Medical Systems, Munich, Germany), consisting of a digital video recorder with an integrated near‐infrared (NIR) light source (energy 0.16 W, wavelength 780 nm) and recorded on video tape (BASF; Ludwigshafen, Germany). The object lens of the camera was covered with a filter (835 nm) to collect NIR radiation and reject visible light. Approximately 2 min after the ICG injection, diode laser therapy was started because of the short half‐life time of ICG in plasma (5 min). The handpiece of the diode laser had an integrated cooling device and a cold transparent ultrasound gel was applied onto the treatment area. Because ICG‐augmented diode laser therapy was used for the treatment of telangiectatic leg veins for the first time, we started with low radiant exposures. The treatment objective was to achieve blanching of vessels without inducing unspecific thermal damage, such as skin burns or scars. Radiant exposure and pulse duration were gradually increased according to the clinical reaction and the first clinical results (dose escalation). Furthermore, two different spot sizes were applied (4 and 6 mm)." Duration of follow‐up: 6 weeks Use of compression: not mentioned
Outcomes	Pain: during each treatment session with PDL and ICG þ DL, pain was documented on a VAS ranging from 0 to 10; 0 represented no pain and 10 equalled extremely severe pain. Photo documentation was done at each visit (Canon EOS D30, 50 mm lens) Side effects: crusts, blistering, oedema, erythema (mild, moderate, and severe), hypopigmentation or hyperpigmentation, telangiectatic matting, and scarring Vessel clearance well as by a blinded observer as follows: no clearance (0%), slight clearance (< 25%), moderate clearance (25% – 50%), good clearance (51% – 75%), or excellent clearance (> 75%) The cosmetic appearance of the treatment area was rated on a scale from 0 (very bad cosmetic appearance) to 10 (very good cosmetic appearance) by the participant and by the blinded observer by means of colour digital photography At each visit, the treatment area was rated by the participants as well as by a blinded observer as follows: no clearance (0%), slight clearance (< 25%), moderate clearance (25% – 50%), good clearance (51% –75%), or excellent clearance (> 75%)
Funding sources	"None"
Declarations of interest	Quote "The Diode laser MeDioStar was provided as a loan by Asclepion, Jena, Germany."
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	The Center for Clinical Studies at the University Hospital Regensburg generated the randomisation list with the software PASS 2008 (NCSS). The allocation of each participant to the respective treatment modality was labelled right/left for ICG‐augmented diode laser therapy or FPDL treatment
Allocation concealment (selection bias)	Low risk	The treatment allocation was deposited in a closed envelope
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	No details given
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Furthermore, the cosmetic appearance of the treatment area was rated on a scale from 0 (very bad cosmetic appearance) to 10 (very good cosmetic appearance) by the patient and by the blinded observer by means of colour digital photography at each visit."
Incomplete outcome data (attrition bias) All outcomes	Low risk	14/15 participants completed each step of the study protocol. 1 participant missed the last visit
Selective reporting (reporting bias)	Unclear risk	No details given
Other bias	Unclear risk	No details given

*Study characteristics*
Methods	Study design: split‐body, randomised study Method of randomisation: coin toss to determine which leg was assigned each treatment Blinding: participant ‐ no, doctor ‐ no Power calculation: not mentioned Total number of participants randomised: 13 participants had each lower limb randomised to receive 1 of 2 sclerosing agents Total number of procedures: 26 Treatment localisation: leg veins Exclusions post‐randomisation: none Number of withdrawals and reasons: none
Participants	Setting: outpatient site Country: USA Gender: women Age: mean 57 years (range 41 ‐ 70) Inclusion criteria: presence of leg veins 0.2 to 0.4 mm in diameter without evidence of feeding reticular veins Exclusion criteria: incompetence at the saphenofemoral or saphenopopliteal junctions
Interventions	Treatment 1: STS 0.25% Treatment 2: chromated glycerin 72% 1 leg of each participant was randomised to receive either STS 0.25% or chromated glycerin 72%, and the other leg received the other agent Duration of follow‐up: ranged from 2 to 6 months Use of compression: not mentioned
Outcomes	Efficacy: vessel clearance (yes, no) assessed by treating physician at follow‐up Adverse events: bruising, swelling, hyperpigmentation (yes, no) assessed by treating physician at follow‐up Pain: assessed by participant at time of injection (yes, no)
Funding sources	No funding source stated
Declarations of interest	No details provided
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A coin toss
Allocation concealment (selection bias)	Unclear risk	No details given
Blinding of participants and personnel (performance bias) All outcomes	High risk	No blinding mentioned. STS and CG have different viscosities that are visible at time of injection
Blinding of outcome assessment (detection bias) All outcomes	Low risk	2 independent experts who were not involved in the treatment
Incomplete outcome data (attrition bias) All outcomes	Low risk	There were no incomplete data
Selective reporting (reporting bias)	Low risk	All specified outcomes were reported
Other bias	Unclear risk	No details given