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

Rawatan untuk telangiektasias dan vena retikular

Declaraciones de intereses de los autores

Versión publicada: 12 octubre 2021 Historial de versiones

https://doi.org/10.1002/14651858.CD012723.pub2

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Abstract

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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.

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

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Rawatan untuk telangiektasias dan vena retikular

Apa itu telangiektasias dan vena retikular?

Telangiektasias (urat labah‐labah) adalah saluran darah kecil yang melebar berhampiran permukaan kulit berukuran diameter kurang dari 1.0 mm. Vena retikular mempunyai diameter kurang dari 3.0 mm dan lebih dalam di dalam kulit. Penyebabnya tidak diketahui, dan boleh menjadi kosmetik semata‐mata, atau boleh mengakibatkan rasa sakit, terbakar atau gatal. Telangiektasias dan vena retikular pada kaki sangat biasa, meningkat seiring dengan usia, dan telah dijumpai sebanyak 41% pada wanita yang berusia lebih dari 50 tahun. Faktor risiko merangkumi sejarah keluarga, kehamilan, trauma tempatan, obesiti dan faktor hormon

Bagaimana telangiektasias dan vena retikular dirawat?

Terdapat beberapa rawatan, seperti skleroterapi, laser, cahaya berdenyut intensif, mikroflebektomi dan termoablasi, tetapi tidak ada yang lebih baik. Kesan sampingan rawatan yang tidak diingini termasuk hiperpigmentasi (kegelapan kulit), matting (telangiektasias baru selepas rawatan), alergi dan kesakitan. Oleh itu, adalah penting untuk mengetahui kesan rawatan ini untuk membantu doktor dan pesakit membuat keputusan yang mana pilihan terbaik untuk mereka.

Apakah yang kami lakukan?

Kami mencari kajian di mana pesakit dipilih secara rawak untuk menerima satu rawatan urat labah‐labah berbanding dengan rawatan palsu, atau jenis rawatan lain. Kami kemudiannya membandingkan hasil‐hasil yang dilaporkan dan merumuskan bukti kajian dari semua kajian. Akhirnya, kami menilai sejauh mana kepastian bukti tersebut. Kami pertimbangkan faktor‐faktor seperti cara kajian dijalankan, saiz kajian, dan konsistensi penemuan merentasi kajian‐kajian. Berdasarkan penilaian, kami membahagikan bukti sebagai kepastian yang sangat rendah, rendah, sederhana atau tinggi.

Apakah yang kami temui?

Kami menemui 35 kajian dengan gabungan 3632 peserta (dicari sehingga 16 Mac 2021). Beberapa kajian membandingkan satu rawatan pada satu kaki dengan rawatan yang lain pada kaki yang lain. Kajian menggunakan pelbagai rawatan yang berbeza dan tidak ada yang melaporkan semua hasil kami. Tidak semua rawatan tersedia disiasat: tidak ada kajian yang mengkaji cahaya berdenyut intensif, termokoagulasi atau mikroflebektomi.

Ejen sklerosis meningkatkan resolusi telangiektasias dan vena retikular jika dibandingkan dengan rawatan palsu, tetapi mengakibatkan lebih kesan sampingan yang tidak diingini (hiperpigmentasi dan matting). Tidak ada faedah yang dapat dilihat pada satu agen sklerosis berbanding yang lain, atau dibandingkan dengan laser, untuk meningkatkan telangiektasias. Berkemungkinan terdapat perbezaan antara rawatan dalam kejadian buruk dan kesakitan. Perbandingan dengan agen lain, polidokanol mungkin menyebabkan kurang sakit. Natrium tetradesil sulfate (STS) boleh menyebabkan hiperpigmentasi, matting dan mungkin lebih banyak kesakitan; buih boleh mengakibatkan lebih banyak matting; rawatan laser boleh menyebabkan kurang hiperpigmentasi. Gabungan laser dengan tambahan skleroterapi boleh menghasilkan resolusi yang lebih baik berbanding dengan skleroterapi sahaja, tetapi boleh menyebabkan lebih banyak kesakitan.

Sejauh manakah keputusan ini boleh dipercayai?

Kami tidak begitu yakin dengan keputusan ini. Kami menurunkan kepastian bukti dengan satu atau dua tahap (dari tinggi hingga sederhana atau rendah). Ini adalah kerana perbezaan dalam reka bentuk kajian, yang bermakna hanya sebilangan kecil kajian dan peserta memberikan maklumat untuk setiap perbandingan rawatan.

Kesimpulan

Kajian lanjut yang direka dengan baik diperlukan untuk meningkatkan keyakinan kami terhadap perbandingan yang dikenal pasti dalam ulasan ini, untuk rawatan lain yang tersedia, dan untuk hasil penting lain, seperti berulang, masa untuk menyelesaikan dan kesan sampingan jangka panjang.

Authors' conclusions

Implications for practice

Sclerosing agents were more effective than placebo for resolution or improvement of telangiectasias, but also cause more adverse events and pain (moderate and low‐certainty evidence). There was no evidence that any sclerosing agent resulted in more resolution or improvement of telangiectasias compared to another or to laser, but there may be some differences in adverse events and pain between some treatments: polidocanol probably causes less necrosis; hypertonic saline probably causes less hyperpigmentation but more pain compared to other sclerosing agents (moderate‐certainty evidence); STS resulted in more hyperpigmentation, matting and probably more pain than other sclerosing agents (moderate‐certainty evidence). Foam agents compared to liquid did not improve resolution, but there may be more matting (moderate‐certainty evidence). Laser treatment may result in less hyperpigmentation compared to any sclerosing agents (moderate‐certainty evidence); combining laser with polidocanol may be more effective to treat telangiectasias and reticular veins compared to polidocanol alone (low‐certainty evidence), but more pain may occur (low‐certainty evidence). There was more improvement of telangiectasias in combining polidocanol with hypertonic glucose compared with hypertonic glucose alone (moderate‐certainty evidence), and no clear differences in adverse events or pain (moderate‐certainty evidence). There was no clear difference in improvement, adverse events or quality of life when comparing sclerotherapy plus compression with sclerotherapy alone. Small numbers of studies and participants in each comparison limited our confidence in the evidence.

Implications for research

Although the treatment of telangiectasias and reticular veins has been conducted by vascular surgeons for several years, there is limited high‐certainty evidence. The lack of standardisation in studies also makes it difficult to analyse and summarise the evidence. We suggest that future trials use a standard methodology. For the intervention standard, the number of sessions is critical for access and to compare data. As most trials evaluated only one intervention session, we suggest that it should be standardised as a unique session to facilitate analysis of the outcome.

Another important topic is the design of the study: some authors compared different individuals and others compare similar regions on different limbs in the same participant. In our view the best design for the study of telangiectasias and reticular veins is the split‐body design, since we are analysing different treatments in the same individual, and the response obtained can be inferred more appropriately for each treatment; we acknowledge that a split‐body design could aggravate the randomisation process. Different study designs can be considered, provided that they are well‐standardised and specified.

We suggest using a single scale to facilitate the interpretation of results for the 'improvement or resolution' outcome and later inclusion of studies in a meta‐analysis. Most of the reviewed studies used a scale of 0 to 4, so we suggest the use of this scale in future trials, with specifications in percentages in order to infer the results obtained with more precision.

When evaluating adverse events it is important for future studies to establish whether they are immediate or late effects. We suggest that immediate adverse events should be evaluated just after the specific session and delayed adverse events arising three to six months after the procedure should also be evaluated in order to study their evolution.

In the studies reviewed here, pain was analysed using the analogue pain scale (0 to 100 mm), and we suggest that standardising the VAS for pain is important for the comparison of results.

Summary of findings

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with placebo	Risk with sclerotherapy	Relative effect (95% CI)	№ of participants/procedures* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 11.88 (4.54 to 31.09)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 12 weeks)	Study population		RR 4.06 (1.28 to 12.84)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 12 weeks)	17 per 1000	68 per 1000 (22 to 216)	RR 4.06 (1.28 to 12.84)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
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
^* Three studies used participants as the unit of analysis and one study used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level due to high clinical heterogeneity of the included studies. ^bWe downgraded by one level due to high clinical heterogeneity of the included studies and wide CI of the included studies (imprecision). ^c We downgraded by two levels due to high clinical heterogeneity of the included studies and only one included study with few participants.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosant agent)	Risk with sclerotherapy (polidocanol)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.94 (0.62 to 1.43)	819 (6 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 16 weeks)	Study population		RR 0.82 (0.52 to 1.27)	859 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 16 weeks)	144 per 1000	118 per 1000 (75 to 183)	RR 0.82 (0.52 to 1.27)	859 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
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
^* Three studies used participants as the unit of analysis and four studies used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level due to wide CIs.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosant)	Risk with sclerotherapy (STS)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 1.71 (1.10 to 2.64)	478 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 24 weeks)	Study population		RR 2.10 (1.14 to 3.85)	323 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 24 weeks)	82 per 1000	173 per 1000 (94 to 318)	RR 2.10 (1.14 to 3.85)	323 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 1 day)	Study population		RR 1.49 (0.99 to 2.25)	409 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 1 day)	275 per 1000	410 per 1000 (273 to 619)	RR 1.49 (0.99 to 2.25)	409 (4 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
^* Two studies used participants as the unit of analysis and four studies used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level due to wide CIs and small number of participants.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosant)	Risk with sclerotherapy (hypertonic saline)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.74 (0.59 to 0.93)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 8 ‐ 12 weeks)	Study population		RR 0.89 (0.58 to 1.36)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 8 ‐ 12 weeks)	215 per 1000	192 per 1000 (125 to 293)	RR 0.89 (0.58 to 1.36)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
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
^* All studies used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level because of high risk of other bias in the included studies. ^bWe downgraded by one level because of wide CIs. ^cWe downgraded by one level because of clinical heterogeneity between included studies.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosing agent)	Risk with sclerotherapy (chromated glycerin)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.49 (0.09 to 2.50)	125 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 5 ‐ 24 weeks)	Study population		RR 0.31 (0.01 to 7.53)	99 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 5 ‐ 24 weeks)	21 per 1000	6 per 1000 (0 to 157)	RR 0.31 (0.01 to 7.53)	99 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
Pain (follow‐up: 1 day)	Study population		RR 1.50 (0.30 to 7.55)	26 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
Pain (follow‐up: 1 day)	154 per 1000	231 per 1000 (46 to 1000)	RR 1.50 (0.30 to 7.55)	26 (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
^* One study used participants as the unit of analysis and one study used the number of procedures as the unit of analysis for each comparison. ^a We downgraded by two levels due to few included studies and participants.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosing agent)	Risk with foam	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 2.12 (0.44 to 10.23)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow up: 5 ‐ 10 weeks)	Study population		RR 6.12 (1.04 to 35.98)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow up: 5 ‐ 10 weeks)	9 per 1000	53 per 1000 (9 to 310)	RR 6.12 (1.04 to 35.98)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
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
^* One study used participants as the unit of analysis and one study used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by two levels due to wide CIs and few participants in the included studies.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy	Risk with laser	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.57 (0.40 to 0.80)	262 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 ‐ 24 weeks)	Study population		RR 1.00 (0.46 to 2.19)	162 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 ‐ 24 weeks)	123 per 1000	123 per 1000 (57 to 270)	RR 1.00 (0.46 to 2.19)	162 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 1 day)	Study population		‐	100 (2 RCTs)	⊕⊝⊝⊝ LOW^b	We were not able to pool the data due to high heterogeneity
Pain (follow‐up: 1 day)	See comment	‐	‐	100 (2 RCTs)	⊕⊝⊝⊝ LOW^b	We were not able to pool the data due to high heterogeneity
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
^* Two studies used participants as the unit of analysis and three studies used the number of procedures as the unit of analysis for each comparison ^aWe downgraded by one level due to wide CIs. ^bWe downgraded by two levels because of few included participants.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy	Risk with laser plus sclerotherapy	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.83 (0.35 to 1.99)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 12 ‐ 16 weeks)	Study population		RR 0.83 (0.21 to 3.28)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 12 ‐ 16 weeks)	18 per 1000	15 per 1000 (4 to 60)	RR 0.83 (0.21 to 3.28)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Pain (follow‐up: 1 day)	Study population		RR 2.44 (1.69 to 3.55)	596 (1 RCT)	⊕⊕⊝⊝ LOW^b	‐
Pain (follow‐up: 1 day)	266 per 1000	649 per 1000 (449 to 944)	RR 2.44 (1.69 to 3.55)	596 (1 RCT)	⊕⊕⊝⊝ LOW^b	‐
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
^* All studies used participants as the unit of analysis. ^aWe downgraded by two levels because of clinical heterogeneity in the included studies and the fact that the two studies were conducted by the same group of investigators. ^bWe downgraded by two levels due to having one included study.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No of Participants^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with hypertonic glucose	Risk with hypertonic glucose plus POL	Relative effect (95% CI)	No of Participants^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.79 (0.62 to 1.01)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 weeks)	Study population		RR 0.78 (0.51 to 1.20)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 weeks)	351 per 1000	273 per 1000 (179 to 421)	RR 0.78 (0.51 to 1.20)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 16 weeks)	Study population		RR 1.02 (0.83 to 1.24)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 16 weeks)	443 per 1000	442 per 1000 (359 to 537)	RR 1.02 (0.83 to 1.24)	191 (2 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; 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
^* All studies used participants as the unit of analysis. ^aWe downgraded one level because of few participants in included studies.

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)^*	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy	Risk with sclerotherapy plus compression	Relative effect (95% CI)	№ of participants (studies)^*	Certainty of the evidence (GRADE)	Comments
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)	RR 0.93 (0.41 to 2.07)	196 (2 studies)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 8 weeks)	Study population		RR 1.84 (0.17 to 19.62)	96 (1 study)	⊕⊕⊝⊝ LOW^b	‐
Adverse events ‐ matting (follow‐up: 8 weeks)	22 per 1000	40 per 1000 (4 to 427)	RR 1.84 (0.17 to 19.62)	96 (1 study)	⊕⊕⊝⊝ LOW^b	‐
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
^*All studies used participants as the unit of analysis. ^aWe downgraded one level because of few participants in included studies. ^bWe downgraded two levels because of few participants and only one included study.

Background

Description of the condition

Telangiectasias, or spider veins, are dilated venules or arterioles (small superficial veins) measuring less than 1.0 mm in diameter and occurring predominantly in the lower extremities (Thomson 2016). Reticular veins have a diameter less than 3.0 mm and are often tortuous and located in the subdermal or subcutaneous tissue (Eklof 2004; Porter 1995). Their cause is unknown. Patients may be asymptomatic or can report pain, burning or itching. Risk factors include family history, pregnancy, local trauma, obesity and hormonal factors (Goldman 2002).

The diagnoses of telangiectasias and reticular veins are clinical and made according to the Clinical, Etiological, Anatomical and Pathophysiological (CEAP) classification system for chronic venous disorders in the lower limb. CEAP classification comprises seven main categories: C0 to C6, and telangiectasias are classified as C1 (Eklof 2004; Lurie 2020).

C0 ‐ no visible or palpable signs of venous disease
C1 ‐ telangiectasia or reticular veins (thread veins)
C2 ‐ varicose veins (diameter of 3.0 mm or more)
C3 ‐ oedema
C4 ‐ changes in the skin and subcutaneous tissue: pigmentation (C4a), eczema (C4a), lipodermatosclerosis (C4b), atrophic blanche (C4b), or corona phlebectatica (C4c)
C5 ‐ healed venous ulcer
C6 ‐ active venous ulcer

The incidence of telangiectasias increases with age (Schwartz 2011). Telangiectasias on the lower limbs are very common and have been found in 41% of women over the age of 50 years (Mujadzic 2015). They can be considered an important aesthetic or cosmetic problem (Hercogova 2002). The presence of telangiectasias may be associated with the insufficiency of major venous systems; approximately 50% to 62% of insufficient perforating veins are found in the presence of telangiectasias (Andrade 2009).

Description of the intervention

Treatments for telangiectasias and reticular veins include sclerotherapy, laser therapy, intense pulsed light treatment, microphlebectomy and thermocoagulation. These techniques can be used in combination to maximise the effects and avoid any damage from the individual techniques. The most common treatment for telangiectasias is sclerotherapy (Schwartz 2011), which is a technique or group of techniques for the destruction of spider veins via the injection of a medication that destroys the vein endothelium, leading to occlusion and subsequent fibrosis. Sclerosing agents are injected into the vein using hypodermic needles until the area around the puncture site blanches, or resistance can be felt. The injection is immediately discontinued if there is extravasation. Individual injections use between 0.1 mL and 0.5 mL of sclerosing agent for each telangiectasias area, although larger volumes of the sclerosing agent are required for larger veins (Worthington‐Kirsch 2005). There are many sclerosing agents and they are generally categorised as detergents or osmotic or chemical irritants. These agents cause endothelial damage that results in blocking the vein (vessel occlusion) and the subsequent disappearance of the vessel being treated (Vitale‐Lewis 2008). Foam sclerotherapy mixes gas and fluid sclerosing agents between two syringes (Tessari 2001). Foam with detergent sclerosants have a more efficient effect as a result of increasing both dwell time and contact area. This increase in efficiency also allows for lower sclerosing doses (Worthington‐Kirsch 2005). Foam is associated with side effects such as microthrombi, matting and transient visual disturbance (Kern 2004). These adverse effects may also occur with conventional sclerotherapy.

Laser therapy is used for the treatment of telangiectasias in people with veins of a diameter less than a 30 gauge needle. Patients with a phobia to needles or allergy to certain sclerosing agents can also benefit from this technique. There are several types of lasers for the treatment of telangiectasias, with varying wavelengths between 532 nm to 1064 nm (Meesters 2014). Treatment with a Nd:YAG 1064 nm laser has shown similar results to sclerotherapy (Parlar 2015). The side effects of laser therapy in the treatment of telangiectasias include erythema, crusting, swelling, and blistering (Tierney 2009). Laser therapy may cause less pain but may also result in complications such as spotting (Mujadzic 2015).

Intense Pulsed Light (IPL) is similar to laser therapy, as high‐intensity light sources emit polychromatic light ranging within the 515 to 1200 nm wavelength spectrum. The treatment of vascular lesions with IPL depends on the type and size of vessels, with angiomas and spider veins demonstrating the best response (Goldberg 2012). There are many clinical indications for treatment with IPL (Raulin 2003). IPL is indicated for the treatment of unwanted hair growth, vascular lesions, pigmented lesions, acne vulgaris, photo damage and skin rejuvenation (Babilas 2010). The negative side effects of IPL include vesicles, burns, erosions, blisters and crust formation, and hypo‐ and hyperpigmentations are also common (Stangl 2008).

Microphlebectomy is performed using hooks which enable venous extraction through minimal skin incisions or even needle punctures. Ambulatory microphlebectomy is indicated in varicose veins in any part of the body, such as arms, the periorbital, abdomen and dorsum (Ramelet 2002).

Thermocoagulation or the radiofrequency energy method is another technique for the treatment of telangiectasias or reticular veins. The method is based on the production of high‐frequency waves, at 4 ΜΗz, transmitted through a thin needle, which causes thermal damage in the veins (Chadornneau 2012).

How the intervention might work

All the above techniques cause lesions in the vascular endothelium and consequently result in the disappearance of the target vessel.

In sclerotherapy, the ideal sclerosant causes full destruction of the vessel wall and minimal thrombus formation. Incomplete destruction of the wall or local thrombosis may lead to recanalisation. The ideal agent would also be nontoxic, easily manipulated, and painless (Worthington‐Kirsch 2005).

Laser and IPL therapies are alternative options but have a high cost compared to sclerotherapy. Both techniques act by exposing the red elements of blood to light energy. Oxyhaemoglobin is the major chromophore in blood vessels, with two absorption bands in the visible light spectrum at 542 nm and 577 nm. Following absorption by oxyhaemoglobin, light energy is converted to thermal energy, which diffuses in the blood vessel, causing photocoagulation, mechanical injury, and finally thrombosis and occlusion of the target vessel (Micali 2016).

Different laser wavelengths can be successfully used to treat vascular lesions. Each type of laser has advantages specific to its wavelength, pulse duration, spot size, and cutaneous cooling profile. The 532 to 595 nm lasers have multiple applications, treating not only telangiectasias, but also pigmentation and even fine wrinkles. The main advantage of using a 1064 nm laser is that its longer wavelength can penetrate more deeply, allowing the effective thermosclerosis of spider veins (Goldman 2004).

A possible advantage of IPL is selective photothermolysis, in which thermal damage is confined to specific epidermal or dermal pigmented targets. Tissues surrounding these targeted structures are spared, potentially reducing nonspecific, widespread thermal injury. There are three main chromophores: haemoglobin, water, and melanin. They have broad absorption peaks of light energy, allowing them to be targeted by a range, as well as a specific wavelength of light (Goldberg 2012).

The advantage of microphlebectomy is minimal or no scarring, no skin necrosis and no residual hyperpigmentation (Ramelet 2002).

Thermocoagulation is a relatively new technology with advantages such as the immediate disappearance of veins, no allergic manifestations, no pigmentation and necrosis, and applicability to all skin types (Chadornneau 2012).

Why it is important to do this review

There is a high prevalence of telangiectasias, or spider veins, and the most common age for presentation is between 30 and 50 years (Ruckley 2008). The incidence increases with age and is an important aesthetic problem (Hercogova 2002). In Brazil, the incidence of telangiectasias in young women is 50% and represents a cosmetic problem for them (Scuderi 2002). A research report from Poland, including women aged between 18 and 60, found a telangiectasias incidence of 27% (Karch 2002). Sclerotherapy, the treatment most often used for telangiectasias, has low costs but is not free from complications. Laser therapy is a safe and efficacious treatment for telangiectasias and can be achieved with multiple lasers (McCoppin 2011). IPL is versatile, which allows the treatment of both vascular and pigmented lesions (Wall 2007). IPL may offer an advantage due to its selective photothermolysis but has a high cost compared to sclerotherapy. Currently, there is a lack of evidence about which of these methods is more effective in the treatment of telangiectasias. There has been a previous Cochrane Review on sclerotherapy for telangiectasias (Schwartz 2011), but none has addressed other methods for the treatment of telangiectasias. This review reports on the evidence available to enable healthcare professionals and consumers to choose the most appropriate treatment method for telangiectasias and reticular veins.

Objectives

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

Methods

Criteria for considering studies for this review

Types of studies

We searched and considered for inclusion all randomised controlled trials (RCTs) and quasi‐RCTs that compared treatment methods for telangiectasias and reticular veins in the lower limb. We included studies that compared individual treatment methods against placebo, or that compared different sclerosing agent, or foam or laser treatment. We also included studies that used a combination of methods.

Types of participants

We considered all participants, both male and female and of all ages, with telangiectasias and reticular veins in the lower limb, confirmed by either the CEAP C1 classification or the clinical assessment of a physician. We excluded people with hereditary haemorrhagic telangiectasias (HHT), mucous telangiectasias, people treated for telangiectasias or superficial vein reflux within the previous 30 days, and people undergoing a simultaneous treatment for telangiectasias and superficial vein reflux.

Types of interventions

We evaluated the following interventions:

Sclerotherapy with any sclerosing agent of any dose or duration (with or without compression treatment);
Laser therapy applied directly to the telangiectasias or reticular veins (any wavelength, any treatment regimen);
Intensive Pulsed Light (IPL) applied directly to the telangiectasias or reticular veins (any wavelength, any treatment regimen);
Thermocoagulation applied directly to the telangiectasias or reticular veins;
Microphlebectomy in reticular veins.

Comparisons:

Sclerotherapy versus placebo;
Sclerotherapy versus sclerotherapy;
Sclerotherapy versus laser therapy;
Sclerotherapy versus IPL;
Sclerotherapy versus thermocoagulation;
Sclerotherapy versus microphlebectomy;
Laser therapy versus placebo;
Laser therapy versus laser therapy;
Laser therapy versus IPL therapy;
Laser therapy versus thermocoagulation;
Laser therapy versus microphlebectomy;
IPL versus placebo;
IPL versus IPL therapy;
IPL versus thermocoagulation;
IPL versus microphlebectomy;
Thermocoagulation versus placebo;
Thermocoagulation versus microphlebectomy;
Any combination of the above treatments versus any combination.

Types of outcome measures

Primary outcomes

Clinically‐ or photographically‐assessed resolution or improvement (or both) of telangiectasias: resolution or improvement were measured by clear diagnostic scales, e.g. vessel clearance < 20%, 20 to 40%, 40 to 60%, 60 to 80%, > 80% (Shamma 2005) or study definitions
Adverse events (including hyperpigmentation, matting, allergy, bruising, anaphylaxis, necrosis of the skin)

Secondary outcomes

Pain during procedure and post‐procedure: pain was measured by clear diagnostic scales during the procedure and 24 hours post‐procedure, e.g. visual analogue pain scale (VAS), used for determining the pain level during laser treatment. Pain is graded by the participant with the help of a coloured gradient and graduated line from 1 to 10 (Kozarev 2011)
Recurrence: recurrence was measured by clear diagnostic scales until 30 days after the procedure, e.g. vessel clearance < 20%, 20 to 40%, 40 to 60%, 60 to 80%, > 80% (Shamma 2005)
Time to resolution (time unit: days)
Quality of life: any scale of quality of life, e.g. Aberdeen Varicose Vein Severity Score (AVVSS) (Smith 1999)

Search methods for identification of studies

Electronic searches

The Cochrane Vascular Information Specialist (CIS) conducted systematic searches of the following databases for RCTs without language, publication year or publication status restrictions:

Cochrane Vascular Specialised Register via the Cochrane Register of Studies (CRS‐Web) (searched 16 March 2021);
Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 2) via the Cochrane Register of Studies Online (CRSO);
MEDLINE (Ovid MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE) (searched 16 March 2021);
Embase Ovid (searched 16 March 2021);
AMED Ovid (searched 16 March 2021);
CINAHL Ebsco (searched 16 March 2021).

The CIS modelled search strategies for other databases on the search strategy designed for CENTRAL. Where appropriate,we combined them with adaptations of the highly sensitive search strategy designed by the Cochrane Collaboration for identifying RCTs and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions Chapter 6, Lefebvre 2011). Search strategies for major databases are provided in Appendix 1.

The Information Specialist searched the following trial registries on 16 March 2021:

World Health Organization International Clinical Trials Registry Platform (who.int/trialsearch);
ClinicalTrials.gov (clinicaltrials.gov).

The authors performed additional searches in LILACS and IBECS databases. The search strategy was designed by the authors and checked by the Cochrane Information Specialist of Cochrane Brazil. See Appendix 2 for details of the search strategy used for the authors' search (searched 17 March 2021).

Searching other resources

We checked the bibliographies of included trials for further references to relevant trials. We contacted specialists in the field, manufacturers and authors of the included trials for any possible unpublished data.

Data collection and analysis

Selection of studies

We examined the titles and abstracts to select the relevant reports after merging the search results and removing duplicate records. Three review authors (LCUN, DGC and RLGF) independently evaluated the trials to determine if they were appropriate to include. We resolved disagreements by discussion within the review team. We then retrieved and examined the full text of the relevant trials for compliance with eligibility criteria. Where a trial did not meet the eligibility criteria, we excluded the trial and documented the reason for exclusion.

Data extraction and management

Three review authors (LCUN, DGC and RLGF) independently extracted and collected data on paper data extraction forms. We resolved disagreements by discussion within the review team. We collected the following information.

Study features: publication details (e.g. year, country, authors); study design; population data (e.g. age, comorbidities, severity of telangiectasias, duration, history of treatments, and responses); details of intervention (e.g. manufacture, material, site of insertion, additional procedures); number of participants randomised into each treatment group; the number of participants in each group who failed treatment; the numbers of participants lost to follow‐up; the duration of follow‐up; cost of treatment; sources of funding; study authors’ potential conflicts of interest.
Outcomes: types of outcomes measured; timing of outcomes.

Assessment of risk of bias in included studies

Three review authors (LCUN, DGC and RLGF), independently assessed the included studies for risks of bias, using Cochrane's risk of bias tool, described in Section 8.5 of the Cochrane Handbook for Systematic Reviews of interventions (Higgins 2011). We planned to resolve disagreements by discussion within the review team, if necessary.

We assessed the following domains and rated them at low, unclear, or high risk of bias:

random sequence generation;
adequate concealment of allocation;
blinding of participants and personnel;
blinding of outcome assessment;
incomplete outcome data;
selective outcome reporting; and
other potential threats to validity.

We reported the assessments for each individual study in the risk of bias tables located in the 'Characteristics of included studies' section. We planned to contact the study author(s) to seek clarification in cases of uncertainty over data.

Measures of treatment effect

We used the risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data with the same scale, or standardised mean difference (SMD) for continuous data with different scales, all with 95% confidence intervals (CIs).

Unit of analysis issues

We considered each participant as the unit of analysis. For trials that considered multiple interventions in the same group, we analysed only the partial data of interest. Studies with a split‐body design were treated as cross‐over trials as recommended in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2021a).

Dealing with missing data

We analysed only the available data and contacted the trial authors to request missing data. We reported dropout rates in the 'Characteristics of included studies' tables of the review, and we used intention‐to‐treat analysis.

Assessment of heterogeneity

We inspected forest plots visually to consider the direction and magnitude of effects and the degree of overlap between confidence intervals. We quantified inconsistency among the pooled estimates using the I² statistic (where I² = ((Q ‐ df)/Q) x 100% where Q is the Chi² statistic, and 'df' represents the degree of freedom). This illustrates the percentage of the variability in effect estimates resulting from heterogeneity rather than sampling error (Deeks 2019). We interpreted the thresholds for the I² statistic as follows: 0 to 30% = low heterogeneity; 30% to 60% = moderate heterogeneity; 60% to 90% = substantial heterogeneity, and more than 90% = considerable heterogeneity (Deeks 2019).

Assessment of reporting biases

We planned to assess the presence of publication bias and other reporting bias using funnel plots if we identified sufficient studies (more than 10) for inclusion in the meta‐analysis (Higgins 2021b).

Data synthesis

We synthesised the data using Review Manager 5 (Review Manager 2020). We planned to use the fixed‐effect model to synthesise the data if there were low to moderate levels of heterogeneity. If there was substantial heterogeneity, we planned to use a random‐effects model. If there was considerable heterogeneity, we planned not to undertake a meta‐analysis but to describe the data narratively in the text. As we identified clinical heterogeneity due to differences in, for example, study designs or sclerosing agents, we used a random‐effects model to synthesize the data.

Subgroup analysis and investigation of heterogeneity

If sufficient data were available, we planned to perform subgroup analyses for the following:

interventions: types of sclerosant, IPL and laser wave lengths; and combination of methods;
participant characteristics: age (e.g. youth (15 years to 24 years), adults (25 years to 64 years) and seniors (65 years and over)), gender and race.

Sensitivity analysis

If an adequate number of studies were available, we planned to perform sensitivity analysis based on allocation concealment (high, low, or unclear) and blinding of outcome assessment (high, low, or unclear). We planned to carry out sensitivity analyses by excluding those trials that we judged to be at high risk of bias according to Higgins 2021b. We were not able to do this, as comparisons did not include sufficient studies.

Summary of findings and assessment of the certainty of the evidence

We prepared summary of findings tables to provide the key information presented in the review comparing treatments in participants with telangiectasias and reticular veins. We prepared summary of findings tables for each comparison at one time point, using the outcomes described in Types of outcome measures:

clinically‐ or photographically‐assessed resolution or improvement, or both, of telangiectasias;
adverse events (hyperpigmentation and matting);
pain during procedure and post‐procedure;
recurrence;
time to resolution;
quality of life.

We assessed the certainty of the evidence for each outcome as high, moderate, low or very low, based on the criteria of risk of bias, inconsistency, indirectness, imprecision, and publication bias, using the GRADE approach (Grade 2004). We based the tables on methods described in Chapters 11 and 12 of the Cochrane Handbook, and justified any departures from the standard methods (Grade 2004; Higgins 2021b).

Results

Description of studies

Results of the search

The searches in the literature databases and trial registries identified 2649 reports, which we reduced to 2279 potentially relevant records after deduplication. We assessed 48 full‐text articles for eligibility, and identified 35 studies which met the review inclusion criteria (Figure 1). We excluded 10 studies and identified three ongoing studies.

Figure 1

Study flow diagram.

Included studies

See Characteristics of included studies.

Type of study

The characteristics of the 35 included studies are shown in Characteristics of included studies. All 35 included studies were RCTs published between 1987 and 2021 (Alos 2006; Bayer 2021; Benigni 1999; Bertanha 2017; Bertanha 2021; Carlin 1987; Christiansen 2015; Goldman 2002; Hamel‐Desnos 2009; Hoss 2020; Ianosi 2019; Kahle 2006; Kern 2004; Kern 2007; Kern 2011; Kern 2012; Klein 2013; Leach 2003; Lupton 2002; McCoy 1999; Moreno‐Moraga 2013; Moreno‐Moraga 2014; Munia 2012; Nguyen 2020; Norris 1989; Ochoa 2021; Ozden 2011; Parlar 2015; Peterson 2012a; Peterson 2012b; Prescott 1992; Rabe 2010; Rao 2005; Schul 2011; Zhang 2012).

Of the 35 studies, nine evaluated participants with telangiectasias (Carlin 1987; Kahle 2006; Leach 2003; Lupton 2002; McCoy 1999; Moreno‐Moraga 2013; Munia 2012; Norris 1989; Ozden 2011), and 26 studied participants with telangiectasias and reticular varicose veins up to 3.0 mm in diameter (Alos 2006; Bayer 2021; Benigni 1999; Bertanha 2017; Bertanha 2021; Christiansen 2015; Goldman 2002; Ochoa 2021; Hamel‐Desnos 2009; Hoss 2020; Ianosi 2019; Kern 2004; Kern 2007; Kern 2011; Kern 2012; Klein 2013; Moreno‐Moraga 2014; Nguyen 2020; Parlar 2015; Peterson 2012a; Peterson 2012b; Prescott 1992; Rabe 2010; Rao 2005; Schul 2011; Zhang 2012).

Only five studies presented a sample size calculation (Bertanha 2017; Kern 2004; Kern 2007; Kern 2011; Kern 2012).

Setting

Ten RCTs were conducted in the USA (Carlin 1987; Goldman 2002; Hoss 2020; Leach 2003; Lupton 2002; Norris 1989; Peterson 2012a; Peterson 2012b; Rao 2005, Schul 2011), five in Switzerland (Kern 2004; Kern 2007; Kern 2011; Kern 2012; Parlar 2015), three in Spain (Alos 2006; Moreno‐Moraga 2013; Moreno‐Moraga 2014), three in Brazil (Bertanha 2017; Bertanha 2021; Munia 2012); four in Germany (Bayer 2021; Kahle 2006; Klein 2013; Rabe 2010), two in France (Benigni 1999; Hamel‐Desnos 2009), one each in China (Zhang 2012), in Turkey (Ozden 2011), in Australia (McCoy 1999), in Canada (Prescott 1992), in Denmark (Christiansen 2015), in Romania (Ianosi 2019), in Vietnam (Nguyen 2020) and in Mexico (Ochoa 2021).

Unit of analysis

Of the 35 included studies, 18 used a split‐body design, comparing groups in an opposite leg or a lower limb quadrant (Benigni 1999; Carlin 1987; Christiansen 2015; Hoss 2020; Ianosi 2019; Kern 2012; Klein 2013; Leach 2003; Lupton 2002; McCoy 1999; Munia 2012; Nguyen 2020; Norris 1989; Ozden 2011; Peterson 2012a; Peterson 2012b; Prescott 1992; Rao 2005). The remaining 17 studies used the participant as the unit of analysis (Alos 2006; Bayer 2021; Bertanha 2017; Bertanha 2021; Goldman 2002; Ochoa 2021; Hamel‐Desnos 2009; Kahle 2006; Kern 2004; Kern 2007; Kern 2011; Moreno‐Moraga 2013; Moreno‐Moraga 2014; Parlar 2015; Rabe 2010; Schul 2011; Zhang 2012).

Study participants

The 35 included studies provided data for 3632 participants. The smallest study included 13 participants (Leach 2003) and the largest included 720 participants (Ochoa 2021). Thirteen studies included up to a maximum of 30 participants (Leach 2003, n = 13; Christiansen 2015, n = 14; Klein 2013, n = 15; Carlin 1987, n = 20; Norris 1989, n = 20; Lupton 2002, n = 20; Nguyen 2020, n = 20; Rao 2005, n = 20; Peterson 2012a, n = 20; Ozden 2011, n = 21; Benigni 1999, n = 24; Hoss 2020, n = 30; Munia 2012, n = 30). Twelve studies included up to 100 participants (Bertanha 2017, n = 93; Kahle 2006, n = 48; Bayer 2021, n = 50; Kern 2012, n = 53; Parlar 2015, n = 56; Schul 2011, n = 58; Prescott 1992, n = 60; Moreno‐Moraga 2013, n = 90; Peterson 2012b, n = 63; Alos 2006, n = 75; McCoy 1999, n = 81; Kern 2007, n = 100). Ten studies included more than 100 participants (Hamel‐Desnos 2009, n = 105; Kern 2011, n = 110; Bertanha 2021, n = 115; Goldman 2002, n = 129; Kern 2004, n = 150; Ianosi 2019, n= 285; Zhang 2012, n = 288; Rabe 2010, n = 316; Moreno‐Moraga 2014, n = 320; Ochoa 2021, n = 720).

All included studies evaluated participants with CEAP C1, telangiectasias or reticular veins (diameter less than 3.0 mm) in the lower limb. Three studies included participants classified CEAP C2, but these data are not included in this review (Goldman 2002; Rao 2005; Zhang 2012).

Most studies (n = 25) evaluated only women (Benigni 1999; Bertanha 2017; Bertanha 2021; Carlin 1987; Christiansen 2015; Hamel‐Desnos 2009; Hoss 2020; Ianosi 2019; Kern 2004; Kern 2007; Kern 2011; Kern 2012; Klein 2013; Leach 2003; Lupton 2002; Moreno‐Moraga 2013; Moreno‐Moraga 2014; McCoy 1999; Munia 2012; Norris 1989; Ozden 2011; Parlar 2015; Peterson 2012a; Prescott 1992; Schul 2011). Eight studies analysed men and women (Alos 2006; Bayer 2021; Ochoa 2021; Nguyen 2020; Peterson 2012b; Rabe 2010; Rao 2005; Zhang 2012). Two studies did not report the gender of the participants (Goldman 2002; Kahle 2006).

Five includes studies did not provide data about the age of the participants (Bayer 2021; Goldman 2002; Kahle 2006; Kern 2011; Rao 2005), and another 10 studies reported the age range without the mean (Bertanha 2017; Bertanha 2021; Carlin 1987; Moreno‐Moraga 2013; Norris 1989; Peterson 2012a; Peterson 2012b; Prescott 1992; Rabe 2010; Zhang 2012). The age of participants ranged from 17 to 80 years.

Twelve studies reported data on the skin photo type by Fitzpatrick’s classification: Photo type I to III (Benigni 1999; Christiansen 2015; Ozden 2011; Parlar 2015); Photo type I to IV (Alos 2006; Bertanha 2017; Klein 2013; Munia 2012; Peterson 2012b); Photo type IV (Moreno‐Moraga 2013; Nguyen 2020); Photo type II to IV (Moreno‐Moraga 2014).

Interventions

There were six sclerosing agents in the included studies: polidocanol (0.25% to 3%), sodium tetradecyl sulfate (STS) (0.25% to 1%), hypertonic saline (20% to 23.4%), chromated glycerin (72%), hypertonic glucose (70%), and dextrose.

Four studies compared any sclerosing agent versus placebo (Carlin 1987; Kahle 2006; Rabe 2010; Zhang 2012). Zhang 2012 and Kahle 2006 compared polidocanol versus placebo. Carlin 1987 compared polidocanol versus STS versus hypertonic saline versus placebo; and Rabe 2010 compared polidocanol versus STS versus placebo).

Nine studies compared sclerosing liquid versus sclerosing liquid (Norris 1989 ‐ polidocanol (0.25%) versus polidocanol (0.50%) versus polidocanol (0.75%) versus polidocanol (1%); Prescott 1992 ‐ hypertonic dextrose versus STS, McCoy 1999 – hypertonic saline versus polidocanol; Goldman 2002 – STS versus polidocanol; Leach 2003 – chromated glycerin versus STS; Rao 2005 – STS versus polidocanol; Peterson 2012b – hypertonic saline versus polidocanol; Bertanha 2017 and Bertanha 2021 – hypertonic glucose versus hypertonic glucose plus polidocanol).

Five studies compared any form of foam (Alos 2006; Benigni 1999; Hoss 2020; Kern 2004; Peterson 2012a). Benigni 1999 and Alos 2006 compared foam versus polidocanol. Kern 2004 compared foam versus polidocanol versus chromated glycerin and Hoss 2020 and Peterson 2012a compared two types of foam.

Ten studies compared laser treatment (Christiansen 2015; Ianosi 2019; Klein 2013; Lupton 2002; Moreno‐Moraga 2013; Moreno‐Moraga 2014; Munia 2012; Nguyen 2020; Ozden 2011; Parlar 2015). Four types of laser were used for the treatment of telangiectasias and reticular veins: long pulsed 1064 nm Nd:YAG laser with different spot sizes, fluency and pulse duration; pulsed dye laser (PDL; 595 nm), potassium titanyl phosphate laser (KTP; 532 nm) and long pulsed 755 nm Nd:YAG. Six studies compared laser versus sclerotherapy (Lupton 2002 – laser versus STS, Munia 2012 – laser versus hypertonic glucose, Moreno‐Moraga 2013 – laser versus polidocanol (foam) versus laser plus polidocanol (foam), Moreno‐Moraga 2014 – laser plus polidocanol (foam) versus polidocanol (foam) and Parlar 2015 – laser versus polidocanol and Ianosi 2019 – laser versus polidocanol versus hypertonic saline). Four studies compared laser versus laser (Klein 2013 – PDL versus Nd:YAG, Christiansen 2015 – Nd:YAG versus Nd‐YAG, Ozden 2011 – KTP versus Nd:YAG, and Nguyen 2020 – Nd:YAG 1064 versus Nd:YAG 755).

Six studies compared additional therapy to the sclerosing agent or different treatment techniques of injecting sclerosing agent: Bayer 2021 and Kern 2007 – sclerotherapy versus sclerotherapy plus compression; Kern 2011 – chromated glycerin versus chromated glycerin plus lidocaine; Kern 2012 – chromated glycerin (standard technique) versus chromated glycerin (two‐step technique), Hamel‐Desnos 2009 – sclerotherapy plus warfarin versus sclerotherapy plus low molecular weight heparin, and Ochoa 2021 – sclerotherapy versus sclerotherapy plus sulodexide.

One study compared sclerotherapy versus compression stockings (Schul 2011).

We did not find eligible studies of the other techniques identified in our protocol (Nakano 2017): Intensive Pulsed Light (IPL), microphlebectomy, or thermocoagulation.

Outcomes

Thirty studies evaluated our primary outcome of improvement or resolution of telangiectasias using photographs and external examination (Alos 2006; Bayer 2021; Bertanha 2017; Bertanha 2021; Carlin 1987; Christiansen 2015; Goldman 2002; Hoss 2020; Ianosi 2019; Kahle 2006; Kern 2004; Kern 2007; Kern 2011; Kern 2012; Klein 2013; Lupton 2002; McCoy 1999; Moreno‐Moraga 2013; Moreno‐Moraga 2014; Munia 2012; Nguyen 2020; Norris 1989; Ozden 2011; Parlar 2015; Peterson 2012b; Prescott 1992; Rabe 2010; Rao 2005; Zhang 2012). Three studies evaluated improvement by direct clinical access (Benigni 1999; Leach 2003; Peterson 2012a). Nineteen studies included participant satisfaction as an outcome (Alos 2006; Benigni 1999; Carlin 1987; Christiansen 2015; Goldman 2002; Kahle 2006; Kern 2004; Kern 2007; Kern 2011; Klein 2013; McCoy 1999; Moreno‐Moraga 2013; Moreno‐Moraga 2014; Munia 2012; Parlar 2015; Peterson 2012b; Rabe 2010; Rao 2005; Zhang 2012).

Two included studies did not mention adverse effects (Kahle 2006; Kern 2011). The main adverse events reported by the other 33 studies are allergy, blistering, bruising, ecchymosis, hyperpigmentation, matting, microthrombosis, necrosis, scarring, swelling, transient neurological abnormality and urticaria. Four studies classified adverse events using different scales (Christiansen 2015; Klein 2013; McCoy 1999; Peterson 2012a).

Twenty‐three studies reported pain as an outcome, using different scales (Alos 2006; Bayer 2021; Bertanha 2017; Bertanha 2021; Carlin 1987; Christiansen 2015; Hoss 2020; Kern 2011; Kern 2012; Klein 2013; Leach 2003; Lupton 2002; McCoy 1999; Moreno‐Moraga 2014; Munia 2012; Nguyen 2020; Norris 1989; Ozden 2011; Parlar 2015; Peterson 2012b; Prescott 1992; Rao 2005; Zhang 2012).

Hamel‐Desnos 2009 did not report any outcomes of interest, as they studied prophylaxis of deep venous thrombosis. We report this as an adverse event.

Only Kern 2007 and Schul 2011 reported quality of life (QoL) as an outcome.

None of the 35 included studies reported on the outcomes of recurrence or time to resolution.

Excluded studies

See Characteristics of excluded studies.

Of the 10 excluded studies, eight were not randomised (Alora 1999; Conrad 1995; Gillet 2017; McDaniel 1999; Omura 2003; Sadick 2003; Weiss 1990; Woo 2003). Spendel 2002 was excluded for not comparing techniques. Dinsdale 2014 was excluded for not separating telangiectasias of the face and limbs.

Ongoing studies

We identified three ongoing studies (NCT04132323; NCT04690803; Zaleski‐Larsen 2017). See Characteristics of ongoing studies.

Risk of bias in included studies

See Figure 2 and Figure 3 for the risk of bias of all included studies summary, and the risk of bias tables of the Characteristics of included studies for further details.

Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Random sequence generation

We ranked random sequence generation (selection bias) at low risk of bias in 15 studies (Alos 2006; Bayer 2021; Benigni 1999; Bertanha 2017; Bertanha 2021; Goldman 2002; Kern 2007; Kern 2011; Kern 2012; Klein 2013; Leach 2003; Moreno‐Moraga 2014; Ozden 2011; Rabe 2010; Schul 2011). We rated two studies at high risk of bias because scheduled appointments for randomisation were used (Moreno‐Moraga 2013), and legs laterality right and left were used (Nguyen 2020). The remaining 18 included studies were considered at unclear risk of bias due to lack of information (Carlin 1987; Christiansen 2015; Ochoa 2021; Hamel‐Desnos 2009; Hoss 2020; Ianosi 2019; Kahle 2006; Kern 2004; Lupton 2002; McCoy 1999; Munia 2012; Norris 1989; Parlar 2015; Peterson 2012a; Peterson 2012b; Prescott 1992; Rao 2005; Zhang 2012).

Allocation concealment

We rated only five included studies at low risk of bias (Bertanha 2017; Bertanha 2021; Goldman 2002; Klein 2013; Moreno‐Moraga 2014). We considered the remaining 30 studies to have an unclear risk of bias, due to lack of information.

Blinding

Selective reporting

Only Leach 2003 was considered at low risk of bias. We considered two studies to be at high risk of bias, as some adverse events were not statistically analysed by sclerosing agent used and descriptive data are not provided (Carlin 1987; Prescott 1992). We judged the remaining 32 included studies to have an unclear risk of bias due to lack of information.

Other potential sources of bias

Only Carlin 1987 was considered to have a high risk of bias because the participants received separate simultaneous treatments and analysis, meaning that the outcomes could have been impacted due to the carry‐over effect. The remaining 34 studies had no clear evidence of other bias.

Effects of interventions

Sclerotherapy (any sclerosing agent) versus placebo

Four studies compared sclerotherapy versus placebo (Carlin 1987; Kahle 2006; Rabe 2010; Zhang 2012). The sclerosing agents used in these four studies were: polidocanol; sodium tetradecyl sulfate (STS); hypertonic saline. We were able to pool the data for these four studies in meta‐analysis. Carlin 1987 was a split‐body study and the data were reported by procedure. See summary of findings Table 1.

Resolution or improvement of telangiectasias

All four included studies showed improvement or resolution of telangiectasias individually, and this benefit from sclerotherapy was also seen on pooling the data (SMD 3.08, 95% CI 2.68 to 3.48; I² = 51%; 613 participants/procedures; moderate‐certainty evidence) (Analysis 1.1). We used a random‐effects model because of the clinical heterogeneity due to different agents used.

Adverse events

Adverse events were studied in three of the included studies (Carlin 1987; Rabe 2010; Zhang 2012). Results showed that hyperpigmentation was more frequent in the group of sclerosing agents compared to the placebo group (RR 11.88, 95% CI 4.54 to 31.09; I² = 0%; 528 participants/procedures; moderate‐certainty evidence). Matting was more frequent in the group of sclerosing agents compared to the placebo group (RR 4.06, 95% CI 1.28 to 12.84; I² = 0%; 528 participants/procedures; moderate‐certainty evidence) (Analysis 1.2).

Studies did not report on bruising, anaphylaxis or necrosis of the skin.

Pain during procedure and post‐procedure

Only Carlin 1987 assessed the outcome pain. There was more pain experienced in the sclerotherapy group compared to the placebo group (SMD 0.70, 95% CI 0.06 to 1.34; 40 procedure; low‐certainty evidence) (Analysis 1.3).

The outcomes 'recurrence', 'time to resolution' and 'quality of life (QoL)' were not reported by any of the four studies in this comparison.

Sclerotherapy (polidocanol) versus any sclerosing agent

Seven studies compared polidocanol versus another sclerosing agent (Carlin 1987; Goldman 2002; Kern 2004; McCoy 1999; Peterson 2012b; Rabe 2010; Rao 2005). Polidocanol was compared to STS (Carlin 1987; Goldman 2002; Rabe 2010; Rao 2005), to chromated glycerin (Kern 2004), and to hypertonic saline (Carlin 1987; McCoy 1999; Peterson 2012b). One study compared different concentrations of polidocanol without a control group (Norris 1989). All included studies were split‐body studies and the data were reported by procedure, except for Goldman 2002, who reported by participant. See summary of findings Table 2.

Resolution or improvement of telangiectasias

We found no clear difference between the polidocanol group compared to the group of other sclerosing agents, for improvement or resolution (SMD 0.01, 95% CI −0.13 to 0.14; I² = 0%; 7 studies, 852 participants/procedures; moderate‐certainty evidence) (Analysis 2.1).

Adverse events

There was no clear difference between the polidocanol group and other sclerosing‐agent groups in cases of hyperpigmentation (RR 0.94, 95% CI 0.62 to 1.43; I² = 84%; 6 studies, 819 participants; moderate‐certainty evidence), or matting (RR 0.82, 95% CI 0.52 to 1.27; I² = 21%; 7 studies, 859 participants/procedures; moderate‐certainty evidence). There were no clear differences in bruising (RR 0.77, 95% CI 0.56 to 1.06; I² = 72%; 4 studies, 558 participants/procedures), microthrombosis (RR 0.96, 95% CI 0.69 to 1.34; I² = 0%; 4 studies, 394 participants/procedures); or allergy between the groups (RR 0.68, 95% CI 0.23 to 2.01; I² = 20%; 4 studies, 472 participants/procedures). There was less necrosis in the polidocanol group compared to the other sclerosing agents group (RR 0.07, 95% CI 0.02 to 0.29; I² = 0%; 4 studies, 558 participants) (Analysis 2.2).

Pain during procedure and post‐procedure

There was less pain in the polidocanol group compared to other sclerosing agent group (SMD −0.26, 95% CI −0.44 to −0.08; I² = 0%; 5 studies, 480 participants/procedures; moderate‐certainty evidence) (Analysis 2.3).

The outcomes 'recurrence', 'time to resolution' and 'QoL' were not available in the seven studies in this comparison.

Sclerotherapy (sodium tetradecyl sulfate (STS)) versus any sclerosing agent

Six studies compared sclerotherapy (sodium tetradecyl sulfate (STS)) with another sclerosing agent (Carlin 1987; Goldman 2002; Leach 2003; Prescott 1992; Rabe 2010; Rao 2005). Sodium tetradecyl sulphate (STS) was compared to polidocanol (Carlin 1987; Goldman 2002; Rabe 2010; Rao 2005), to chromated glycerin (Leach 2003) and to hypertonic dextrose (Prescott 1992). Carlin 1987; Leach 2003; Prescott 1992; Rao 2005 were split‐body studies and the data were reported by procedure. See summary of findings Table 3.

Resolution or improvement of telangiectasias

There was no clear difference in improvement or resolution between the STS group or other agents group (SMD −0.07, 95% CI −0.25 to 0.11; I² = 0%; 4 studies, 473 participants/procedures; moderate‐certainty evidence) (Analysis 3.1).

Adverse events

There were more cases of hyperpigmentation (RR 1.71, 95% CI 1.10 to 2.64; ; I² = 65%; 4 studies, 478 participants/procedures; moderate‐certainty evidence), and matting (RR 2.10, 95% CI 1.14 to 3.85; I² = 0%; 2 studies, 323 participants; moderate‐certainty evidence) in the STS group compared with the other sclerosing agents group. There was more bruising (RR 1.62, 95% CI 1.14 to 2.30; I² = 53%; 3 studies, 418 participants/procedures) and necrosis (RR 16.31, 95% CI 3.14 to 84.79; I² = 0%; 2 studies, 392 participants/procedures) in the STS group. There was little or no difference in reports of allergy (RR 1.38, 95% CI 1.01 to 1.88; I² = 0%; 3 studies, 452 participants/procedures) or microthrombosis (RR 1.04, 95% CI 0.78 to 1.39; 1 study, 129 participants/procedures) (Analysis 3.2).

Pain during procedure and post‐procedure

STS probably results in more pain compared with other sclerosing agents (RR 1.49, 95% CI 0.99 to 2.25; I² = 45%; 4 studies, 409 participants; moderate‐certainty evidence) (Analysis 3.3).

The outcomes 'recurrence', 'time to resolution' and 'QoL' were not reported in the six studies in this comparison.

Sclerotherapy (hypertonic saline) versus any sclerosing agent

We included three studies in this comparison (Carlin 1987; McCoy 1999; Peterson 2012b). The sclerosing agent hypertonic saline was compared to STS (Carlin 1987) and to polidocanol (Carlin 1987; McCoy 1999; Peterson 2012b). All included studies were split‐body studies and the data were reported by procedure. See summary of findings Table 4.

Resolution or improvement of telangiectasias

There was no clear difference in improvement or resolution of telangiectasias between the hypertonic saline group and the other sclerosing agent group (SMD 0.01, 95% CI −0.20 to 0.22; I² = 0%; 3 studies, 348 participants/procedures; moderate‐certainty evidence) (Analysis 4.1).

Adverse events

There were fewer cases of hyperpigmentation in the hypertonic saline group than in another‐sclerosing‐agent group or the polidocanol subgroup (RR 0.74, 95% CI 0.59 to 0.93; I² = 0%; 2 studies, 288 participants/procedures; moderate‐certainty evidence) (Analysis 4.2).

There was no clear difference in matting between the hypertonic‐saline group and another‐sclerosing‐agent group (RR 0.89, 95% CI 0.58 to 1.36; 2 studies; I² = 0%; 288 participants/procedures; moderate‐certainty evidence) (Analysis 4.2).

No other adverse effects have been reported in the included studies.

Pain during procedure and post‐procedure

More pain was reported in the hypertonic‐saline group than in another‐sclerosing‐agent group (SMD 6.22, 95% CI 5.70 to 6.73; I² = 0%; 3 studies, 348 participants/procedures; moderate‐certainty evidence) (Analysis 4.3).

The outcomes 'recurrence', 'time to resolution' and 'QoL' were not reported in the three studies in this comparison.

Sclerotherapy (chromated glycerin) versus any sclerosing agent

Four studies used chromated glycerin (Kern 2004; Kern 2011; Kern 2012; Leach 2003). Two studies analysed chromated glycerin as a sclerosing agent and compared it with POL (Kern 2004) and STS (Leach 2003). Kern 2012 and Leach 2003 were both split‐body studies and the data were reported by procedure. See summary of findings Table 5.

The two further studies compared chromated glycerin versus chromated glycerin with different techniques, and assessed only pain, and so were not part of the meta‐analysis (Kern 2011; Kern 2012).

Resolution or improvement of telangiectasias

There was no difference in improvement or resolution of telangiectasias in the chromated glycerin group compared to the other sclerosing agent group (SMD 0.45, 95% CI −0.11 to 1.02; I² = 44%; 2 studies, 125 participants/procedures; low‐certainty evidence) (Analysis 5.1).

Adverse events

There were no clear differences in hyperpigmentation (RR 0.49, 95% CI 0.09 to 2.50; I² = 0%; 2 studies, 125 participants/procedures; low‐certainty evidence), or matting (RR 0.31, 95% CI 0.01 to 7.53; 1 study, 99 participants/procedures; low‐certainty evidence) between the chromated‐glycerin group compared to the other‐sclerosing‐agent group. There were no differences in bruising (RR 0.14, 95% CI 0.02 to 1.00; 1 study, 26 participants/procedures) or microthrombosis (RR 1.32, 95% CI 0.45 to 3.87; 1 study, 99 participants/procedures) between analysed groups (Analysis 5.2).

Pain during procedure and post‐procedure

There were no clear differences in pain (RR 1.50, 95% CI 0.30 to 7.55; 1 study, 26 participants/procedures; low‐certainty evidence) between the chromated glycerin group compared to another sclerosing agent (Analysis 5.3).

Kern 2011 studied pure chromated glycerin versus chromated glycerin plus 1% lidocaine, and demonstrated that a combination of chromated glycerin plus lidocaine resulted in less pain than chromated glycerin alone. Kern 2012 studied conventional sclerotherapy with chromated glycerin versus sclerotherapy with chromated glycerin in two steps. Kern 2012 concluded that the two‐step technique resulted in less pain than the conventional sclerotherapy technique.

The outcomes 'recurrence', 'time to resolution' and 'QoL' were not available in the studies in this comparison.

Foam versus sclerotherapy (any sclerosant agent)

Foam was compared to polidocanol in three studies (Alos 2006; Benigni 1999; Kern 2004).

We were able to pool data from two studies with 187 participants (Benigni 1999; Kern 2004). Benigni 1999 was a split‐body study and the data were reported by procedure. See summary of findings Table 6.

Resolution or improvement of telangiectasias

There was no clear difference in improvement or resolution of telangiectasias between the foam group and the other‐sclerosing‐agents group (SMD 0.04, 95% CI −0.26 to 0.34; I² = 0%; 2 studies, 187 participants/procedures; low‐certainty evidence) (Analysis 6.1).

Alos 2006 studied 75 participants (150 procedures) comparing polidocanol and foam. Three months after treatment, total occlusion of the vein was observed in 94% of foam interventions and 54% of polidocanol interventions (P < 0.001). Differences in the percentages of total efficacy for the two study groups were reported as statistically significant.

Adverse events

There was no clear difference in hyperpigmentation between the foam group and the other‐sclerosing‐agents group (RR 2.12, 95% CI 0.44 to 10.23; I² = 0%; 2 studies, 187 participants/procedures; low‐certainty evidence). There were more cases of matting in the foam group compared with the other sclerosing agents group (RR 6.12, 95% CI 1.04 to 35.98; I² = 0%; 2 studies, 187 participants/procedures; low‐certainty evidence). There was no difference in bruising (RR 0.60, 95% CI 0.35 to 1.04; 1 study, 40 participants/procedures), or microthrombosis (RR 1.39, 95% CI 0.70 to 2.76; I² = 0%; 2 studies, 187 participants/procedures;) in the included studies (Analysis 6.2).

Alos 2006 reported that no complications occurred at the time of sclerotherapy. Inflammation was present in 25.3% of the foam group and 9.5% of the polidocanol liquid intervention group (P = 0.08). This study reported that the percentage of pigmentation was significantly higher at all follow‐up intervals for the foam group.

Pain during procedure and post‐procedure

There was no clear difference in pain between the foam group compared to the other‐sclerosing‐agents group (SMD −0.10, 95% CI −0.44 to 0.24; 1 study, 147 participants/procedures; low‐certainty evidence) (Analysis 6.3).

Benigni 1999, Kern 2004 and Alos 2006 did not report 'recurrence', 'time to resolution' or 'QoL'.

Laser versus sclerotherapy (any sclerosing agent)

Five studies were included in this comparison (Ianosi 2019; Lupton 2002; Moreno‐Moraga 2013; Munia 2012; Parlar 2015). Laser was compared to STS (Lupton 2002), hypertonic glucose, (Munia 2012), and polidocanol (Ianosi 2019; Moreno‐Moraga 2013; Parlar 2015). Ianosi 2019; Lupton 2002 and Munia 2012 were split‐body studies and the data were reported by procedure. See summary of findings Table 7.

Resolution or improvement of telangiectasias

There were no clear differences in improvement or resolution of telangiectasias in the laser group compared to the any‐sclerosing‐agent group (SMD −0.09, 95% CI −0.25 to 0.07; I² = 0%; 5 studies, 593 participants/procedures;moderate‐certainty evidence) (Analysis 7.1).

Adverse events

There were fewer hyperpigmentation events in the laser group than in the any‐sclerosing‐agent group (RR 0.57, 95% CI 0.40 to 0.80; I² = 0%; 4 studies, 262 participants/procedures; moderate‐certainty evidence) (Analysis 7.2).

There were no clear differences between the laser group compared to the any‐sclerosing‐agent group in matting (RR 1.00, 95% CI 0.46 to 2.19; I² = 0%; 2 studies, 162 participants/procedures;moderate‐certainty evidence). There were no differences in bruising (RR 0.79, 95% CI 0.60 to 1.04; 1 study, 40 participants/procedures), or necrosis (RR 1.60, 95% CI 0.20 to 12.74; I² = 0%; 3 studies, 202 participants/procedures) in the included studies (Analysis 7.2).

Pain during procedure and post‐procedure

Due to the high heterogeneity among the included studies (I² = 94%), we present the results qualitatively (Analysis 7.3).

In Lupton 2002, 70% of 20 participants reported mild treatment pain associated with both methods (laser and conventional sclerotherapy). Munia 2012 reported mild treatment pain in 7/30 participants in the laser group versus 26/30 in the sclerotherapy group; very painful in 20/30 participants versus 4/30 participants respectively in laser and sclerotherapy groups; and extremely painful in 3/30 participants in the laser group versus 0/30 in the sclerotherapy group.

The outcomes 'recurrence', 'time to resolution' and 'QoL' were not reported by the four studies in this comparison.

Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol)

Moreno‐Moraga 2013 and Moreno‐Moraga 2014 compared a combination technique with laser neodymium: YAG (Nd:YAG) plus polidocanol (foam) sclerotherapy versus only sclerotherapy with polidocanol (foam). See summary of findings Table 8.

Resolution or improvement of telangiectasias

There was more improvement or resolution in telangiectasias and reticular veins in the laser‐plus‐sclerotherapy group compared to the sclerotherapy group (SMD 5.68, 95% CI 5.14 to 6.23; I² = 19%; 2 studies, 710 participants; low‐certainty evidence) (Analysis 8.1).

Adverse events

There were no clear differences in hyperpigmentation (RR 0.83, 95% CI 0.35 to 1.99; I² = 0%; 2 studies, 656 participants; low‐certainty evidence), or matting (RR 0.83, 95% CI 0.21 to 3.28; I² = 0%; 2 studies, 656 participants; low‐certainty evidence) in the combination‐technique group compared to the sclerosing‐agent‐alone group. Studies did not report on bruising, anaphylaxis or necrosis of the skin (Analysis 8.2).

Pain during procedure and post‐procedure

Only Moreno‐Moraga 2014 reported on pain. There was more pain in the combination‐technique group compared to the sclerosing‐agent‐alone group (RR 2.44, 95% CI 1.69 to 3.55; 1 study, 596 participants; low‐certainty evidence).

Moreno‐Moraga 2013 and Moreno‐Moraga 2014 did not report 'recurrence', 'time to resolution' or 'QoL'.

Sclerotherapy (hypertonic glucose plus polidocanol) versus hypertonic glucose

Two studies (191 participants) analysed hypertonic glucose as a sclerosing agent and compared hypertonic glucose plus polidocanol versus hypertonic glucose (Bertanha 2017; Bertanha 2021). See summary of findings Table 9.

Resolution or improvement of telangiectasias

There was more improvement or resolution of telangiectasias in the combination‐technique group (polidocanol plus hypertonic glucose) when compared with the hypertonic‐glucose group (SMD 0.79, 95% CI 0.50 to 1.09; I² = 0%; 2 studies, 191 participants; moderate‐certainty evidence) (Analysis 9.1).

Adverse events

There were no clear differences in hyperpigmentation (RR 0.79, 95% CI 0.62 to 1.01; I² = 0%; 2 studies, 191 participants; moderate‐certainty evidence); matting (RR 0.78, 95% CI 0.51 to 1.20; I² = 0%; 2 studies, 191 participants; moderate‐certainty evidence) when comparing the combination technique (polidocanol plus hypertonic glucose) with the hypertonic‐glucose group (Analysis 9.2).

No other adverse events were reported.

Pain during procedure and post‐procedure

There were no clear differences in pain (RR 1.02, 95% CI 0.83 to 1.24; I² = 0%; 2 studies, 191 participants; moderate‐certainty evidence), when comparing the combination‐technique group (polidocanol plus hypertonic glucose) with the hypertonic‐glucose group (Analysis 9.3).

Bertanha 2017 and Bertanha 2021 did not evaluate 'recurrence', 'time to resolution' or 'QoL'.

Compression after sclerotherapy

Kern 2007 and Bayer 2021 studied the effect of compression after sclerotherapy. Both groups underwent sclerotherapy, then one group was randomised to go without compression stockings (WCS) and one group was randomised to use compression stocking (23 to 32 mmHg).

Resolution or improvement of telangiectasias

There was no difference in improvement or resolution in the compression‐after‐sclerotherapy group compared to the WCS group (SMD 0.09, 95% CI −0.19 to 0.37; I² = 0%; 2 studies, 196 participants; moderate‐certainty evidence) (Analysis 10.1).

Adverse events

There were no clear differences in adverse events between the compression‐after‐sclerotherapy group and the WCS group for hyperpigmentation (RR 0.93, 95% CI 0.41 to 2.07; ; I² = 0%; 2 studies, 196 participants; moderate‐certainty evidence); or matting (RR 1.84, 95% CI 0.17 to 19.62; 1 study, 96 participants; low‐certainty evidence) (Analysis 10.2).

Quality of life (QoL)

There was no difference in QoL scores (SF‐36 questionnaires) between the compression‐after‐sclerotherapy group and the WCS group (SMD −0.02, 95% CI −0.42 to 0.39; 1 study, 93 participants; low‐certainty evidence) (Analysis 10.3).

The outcomes 'pain', 'recurrence' and 'time to resolution' were not reported by Kern 2007 or Bayer 2021.

Foam (STS plus air) versus foam (STS plus CO₂)

Only Peterson 2012a studied different types of foam combined with air or CO₂.

Resolution or improvement of telangiectasias

Peterson 2012a reported no difference in improvement or resolution in reticular veins when the STS‐plus‐air group (20 participants) was compared with the STS‐plus‐CO₂ group (20 participants). The study authors did not explore the resolution of telangiectasias, since these veins were treated with glycerin solution.

Adverse events

Peterson 2012a reported there was no clear difference in adverse events between the STS‐plus‐air group and the STS‐plus‐CO₂ group. Coagulums were presented in 55% of CO₂ foam and 60% of RA foam (P = 0.75).

Peterson 2012a did not report 'pain', 'recurrence', 'time to resolution' or 'QoL'.

Foam (POL plus 1:2 air) versus foam (POL plus 1:4 air)

Only Hoss 2020 studied foam with polidocanol combined with different proportions of air (1:2 and 1:4).

Resolution or improvement of telangiectasias

The study authors reported a mean improvement between 0% and 50% at day 21 and 26% to 75% at day 90, with no significant difference in the resolution or improvement of the reticular veins between the 1:2 ratio versus the 1:4 ratio groups.

Adverse events

The study authors found no statistically significant difference for adverse events between the 1:2 and 1:4 ratio groups at any time point. Most participants rated pain during injection (1.73 vs 1.70), current pain (0.80 vs 1.07), itching (0.57 vs 0.83), swelling (0.93 vs 1.37), and redness (1.53 vs 1.83) as none, minimal, or mild in both the 1:2 and 1:4 ratio groups, respectively.

Laser versus laser

We included four studies for a qualitative analysis (Christiansen 2015; Klein 2013; Nguyen 2020; Ozden 2011). We did not pool data in a meta‐analysis because they were isolated studies using different laser techniques that cannot be pooled.

Ozden 2011 studied potassium‐titanyl‐phosphate (KTP) versus Nd:YAG.

Study authors reported a significant positive correlation in the Nd:YAG group compared to the KTP laser group for outcome improvement or resolution in veins of 1.0 mm to 3.0 mm. There was no difference between KTP and Nd:YAG laser for telangiectasias and veins of less than 1.0 mm. They reported that both laser treatments were well‐tolerated by all participants, with no reported serious adverse events. Urticaria appeared in most participants immediately after treatment, but resolved within a few hours. The average level of pain reported by participants during treatment with the KTP laser was 3.1 (95% CI 2.23 to 3.97) compared with 6.89 (95% CI 5.63 to 8.15) for the Nd:YAG treatment.

Klein 2013 studied indocyanine green (ICG)‐augmented diode laser therapy (808 nm) versus diode laser without ICG and pulsed dye laser (PDL).

The mean clearance rate of resolution of telangiectasias for PDL therapy after three months was 2.07 (95% CI 1.07 to 3.07) (moderate clearance), as rated by the participants, and 0.78 (95% CI −0.11 to 1.67) (no difference) as rated by the blinded investigator. The rate of resolution of telangiectasias for ICG diode laser therapy alone was 0.3, as rated by the blinded investigator. Hypopigmentation and hyperpigmentation were seen in 32% of participants.

Christiansen 2015 studied different parameters of Nd:YAG laser. The application of Nd;YAG laser with fixed (FF) and adjustable (JF) parameters has been studied. There was no difference in improvement or resolution with FF or JF parameters.

There was a higher incidence of adverse events (hyperpigmentation) at 39.3% versus 28.6% in the FF group (P = 0.05).

Pain was not mentioned by Christiansen 2015.

Nguyen 2020 studied long pulsed 1064 nm (LP 1064) versus 755 nm (LP 755). There was no difference in improvement or resolution of telangiectasias or reticular veins (71.87% in LP 1064 versus 71.69% in LP 755, P = 0.99). All participants reported painful sensation. The study reported that pain caused by LP 1064 with a median of 7 (range 2 to 8) was significantly higher than pain caused by LP 755, with a median of 5 (range 2 to 8; P = 0.001). Hyperpigmentation occurred in half or more of the participants at one month of observation, with no significant difference between the two groups (63.64% and 50% for LP 1064 and LP 755, respectively; P = 0.36).

The preplanned outcomes 'recurrence', 'time to resolution' and 'QoL' were not reported by the studies in this comparison.

Different concentrations of polidocanol

Norris 1989 compared different concentrations of polidocanol, 0.25%, 0.50%, 0.75%, and 1.0% in 20 participants. There were no differences among the four dosages for improvement or resolution of telangiectasias, itching, or neovascularisation. Polidocanol concentrations of 0.75% and 1% showed more hyperpigmentation (P = 0.15 and P = 0.07, respectively).

Compression versus sclerotherapy

Schul 2011 compared compression stockings (20 to 30 mmHg) versus sclerotherapy in 58 participants with symptomatic reticular veins and telangiectasias. They only reported on quality of life, measured using an Aberdeen Varicose Vein Questionnaire. The study reported that compression stockings can offer relief of aching (P < 0.001), pain (P = 0.002); and cramping (P = 0.003) in participants with isolated refluxing reticular veins and telangiectasias. Sclerotherapy of these smaller vessels offers superior relief of aching (P < 0.001), pain (P < 0.001), swelling (P < 0.001), leg cramps (P < 0.05), and presence of symptoms at rest.

Sclerotherapy plus sulodexide versus sclerotherapy

Ochoa 2021 compared sclerotherapy with POL plus sulodexide versus sclerotherapy in 609 participants with telangiectasias and reticular veins. The study authors reported there was no difference in improvement or resolution between sulodexide group and control group after three months (76% in sulodexide group and 73% in control group, P = 0.61). There was less hyperpigmentation in the sulodexide group compared with the control group at one month (10.7% in sulodexide group and 18.2% control group; P < 0.01).

Sclerotherapy plus warfarin versus sclerotherapy plus nadroparin

Hamel‐Desnos 2009 compared sclerotherapy with POL plus warfarin versus sclerotherapy with POL plus nadroparin in 105 participants with thrombophilia. There was no thromboembolic event in any group. The rate of inflammatory reactions (1.5%) and superficial thrombophlebitis (1.5%) did not exceed that found in the general population (4.5%). They did not report on any other outcomes of interest.

Reporting bias, subgroup and sensitivity analyses

We were unable to assess reporting bias using funnel plots, as none of the meta‐analyses included 10 or more studies.

We were unable to perform the planned subgroup analyses for interventions of participant characteristics, because there were no data available in the selected studies.

We planned to carry out sensitivity analyses by excluding those trials that we judged to be at high risk of bias for allocation concealment or blinding of outcome assessment. No studies were at high risk of allocation bias. Kern 2012 was at high risk from blinding of outcome assessment, but was not included in any meta‐analysis.

Discussion

Summary of main results

We identified 35 randomised controlled trials (RCTs) with a total of 3632 participants, which used a variety of different methods to treat telangiectasias and reticular veins. None of the included studies reported on recurrence or time to resolution, and most did not report on quality of life (QoL).

There is moderate‐certainty evidence that sclerosing agents are more effective for resolution or improvement of telangiectasias compared to a placebo, but that they also have more adverse effects. The observed adverse effects were relatively minor, such as hyperpigmentation and matting. There may be increased pain caused by the sclerosing agent that cannot be attributed solely to the injection of the agent (low‐certainty evidence). See summary of findings Table 1.

We did not find reliable evidence for the superiority of any of the various sclerosing agents studied for resolution or improvement of telangiectasias (moderate‐certainty evidence). See summary of findings Table 2. Polidocanol and hypertonic saline probably cause less necrosis and hyperpigmentation respectively, when compared to other sclerosing agents (moderate‐certainty evidence). STS resulted in more hyperpigmentation, matting (moderate‐certainty evidence), bruising and necrosis, and probably more pain(moderate‐certainty evidence), than the other sclerosing agents. See summary of findings Table 3. Hypertonic saline may result in more pain compared to other sclerosing agents (moderate‐certainty evidence). See summary of findings Table 4. There were few studies with glycerin and glucose and no differences in resolution or improvement of telangiectasias, adverse events or pain were detected (low‐certainty evidence). See summary of findings Table 5.

The use of foam did not affect resolution compared to liquid polidocanol (low‐certainty evidence), and no clear differences were detected in hyperpigmentation, bruising, microthrombus or pain (low‐certainty evidence). There may be more matting in the foam group compared to other sclerosing agents (low‐certainty evidence). See summary of findings Table 6.

Laser treatment had similar improvement or resolution of telangiectasias compared to the any‐sclerosing‐agent group (moderate‐certainty evidence). Laser treatment may result in less hyperpigmentation compared to any sclerosing agents (moderate‐certainty evidence), but no differences were detected for matting, bruising or necrosis compared to other sclerosing agents. Due to the high heterogeneity among the included studies, the pain data are presented qualitatively. See summary of findings Table 7.

The combination technique laser plus polidocanol may be more effective to treat telangiectasias and reticular veins compared to polidocanol alone (low‐certainty evidence). There were no differences in hyperpigmentation and matting (low‐certainty evidence), but more pain may occur after laser plus polidocanol (low‐certainty evidence). See summary of findings Table 8.

The combination technique hypertonic glucose plus polidocanol was probably more effective to treat telangiectasias and reticular veins compared to hypertonic glucose alone (moderate‐certainty evidence). There were no differences in hyperpigmentation, matting or pain (moderate‐certainty evidence). See summary of findings Table 9.

The combination technique sclerotherapy plus compression did not affect improvement or resolution of telangiectasias compared to sclerotherapy alone (moderate‐certainty evidence). No clear differences were detected for hyperpigmentation (moderate‐certainty evidence), matting or QoL (low‐certainty evidence). See summary of findings Table 10.

Overall completeness and applicability of evidence

We did not find any studies comparing intensive pulsed light (IPL), thermocoagulation and microphlebectomy with other techniques for treatment of telangiectasias and reticular veins. The included studies did not present data on time to resolution, recurrence or QoL. We found different study designs using either body parts (opposite leg or a lower limb quadrant), or the individual participant as a research unit, which makes it difficult to analyse the data together.

Quality of the evidence

We used GRADE to evaluate the certainty of the evidence (Grade 2004).

Sclerotherapy versus placebo

See summary of findings Table 1. The certainty of the evidence for the outcome 'resolution or improvement of telangiectasias' was downgraded by one level to moderate because of inconsistency due to the clinical heterogeneity of the included studies. We downgraded by one level to moderate for adverse events (hyperpigmentation and matting) because of clinical heterogeneity and imprecision due to the wide of confidence intervals (CIs). The certainty of the evidence for pain was downgraded by two levels to low because of clinical heterogeneity, the small sample size and the data being from a single study.

Polidocanol versus any sclerosing agent

See summary of findings Table 2. The certainty of the evidence for the outcomes 'resolution or improvement of telangiectasias', adverse events (hyperpigmentation and matting), and pain was downgraded by one level due to a wide CI.

STS versus any sclerosing agent

See summary of findings Table 3. The certainty of the evidence for the outcomes 'resolution or improvement of telangiectasias', adverse events (hyperpigmentation and matting), and pain was downgraded by one level to moderate because of imprecision, due to the wide CI and few included participants.

Hypertonic saline versus any sclerosing agent

See summary of findings Table 4. The certainty of the evidence for the outcome 'resolution or improvement of telangiectasias' was downgraded by one level to moderate because of risk of bias in the included studies. The certainty of the evidence for adverse events (hyperpigmentation and matting) was downgraded by one level to moderate because of imprecision due to the wide CI. Pain was downgraded by one level to moderate due to the clinical heterogeneity of the included studies.

Chromated glycerin versus any sclerosing agent

See summary of findings Table 5. The certainty of the evidence for the outcomes 'resolution or improvement of telangiectasias', adverse events (hyperpigmentation, matting) and pain, was downgraded by two levels to low because of few included participants.

Foam versus any sclerosing agent

See summary of findings Table 6. The certainty of the evidence for the outcomes 'resolution or improvement of telangiectasias', adverse events (hyperpigmentation and matting), and pain was downgraded by two levels to low because of imprecision, due to the wide CI and few participants in the included studies.

Laser versus sclerotherapy

See summary of findings Table 7. The certainty of the evidence for the outcome 'resolution or improvement of telangiectasias', adverse events (hyperpigmentation and matting) was downgraded by one level to moderate because of imprecision due to the wide CI. Pain was downgraded by two levels because of few participants in the included studies.

Laser plus POL versus POL

See summary of findings Table 8. The certainty of the evidence for the outcome 'resolution or improvement of telangiectasias', and adverse events (hyperpigmentation and matting), was downgraded by two levels to low because of inconsistency due to the clinical heterogeneity between the included studies and the fact that the two studies in this comparison were conducted by the same group of investigators. Pain was downgraded by two levels to low because there was only one included study.

Hypertonic glucose plus POL versus hypertonic glucose

See summary of findings Table 9. The certainty of the evidence for all outcomes,'resolution or improvement of telangiectasias', adverse events (hyperpigmentation and matting) and pain was downgraded by one level to moderate because of few participants in the included studies.

Sclerotherapy plus compression versus sclerotherapy

See summary of findings Table 10. The certainty of the evidence for 'resolution or improvement of telangiectasias' and hyperpigmentation was downgraded by one level to moderate because of few participants in the included studies. Matting and QoL were downgraded two levels because of few participants and only one included study.

Potential biases in the review process

We have attempted to include all available RCTs in this review, but it is possible that some studies have not been included, especially from the grey literature. We adhered to the inclusion and exclusion criteria prespecified in the protocol in order to limit subjectivity (Nakano 2017). We made efforts to obtain additional relevant data from study authors but were unable to do so for all. If we can source supplementary data, we will consider them in future updates. Two review authors selected studies in duplicate, independently, to reduce potential bias of the review process. Three review authors independently extracted and collected data, and assessed risks of bias of the included studies to reduce potential bias in the review process. We were not able to include all studies in a meta‐analysis.

Agreements and disagreements with other studies or reviews

Schwartz 2011 studied sclerosing agents for the treatment of telangiectasias, but they evaluated neither reticular veins nor adverse events in their review. In agreement with our findings, Schwartz 2011 reported that no sclerosing agent studied was more effective than the others, with a low quality of evidence due to a lack of eligible studies.

Smith 2015 studied the management of reticular veins and telangiectasias of the lower limb, by sclerotherapy, radiofrequency and laser. They concluded that sclerotherapy was the most effective method for the treatment of reticular veins and telangiectasias. This was a narrative rather than a systematic review, and included all types of studies.

In the Management of Chronic Venous Disease Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS), Wittens 2015 recommended that liquid sclerotherapy should be considered for treating telangiectasias and reticular veins. This recommendation was made based on studies that were included in our review (Kahle 2006, Rabe 2010, Zhang 2012). European guidelines for sclerotherapy in chronic venous disorders (Rabe 2014) also recommends sclerotherapy as a treatment for telangiectasias.

Yiannakopoulou 2016 studied the adverse events of sclerosing agents. Hyperpigmentation and matting were the most frequently‐reported local adverse events in sclerotherapy, a finding supported by our review.

Figure 1

Study flow diagram.

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Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

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Analysis 1.1

Comparison 1: Sclerotherapy (any sclerosing agent) versus placebo, Outcome 1: Resolution or improvement of telangiectasias

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Analysis 1.2

Comparison 1: Sclerotherapy (any sclerosing agent) versus placebo, Outcome 2: Adverse events

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Analysis 1.3

Comparison 1: Sclerotherapy (any sclerosing agent) versus placebo, Outcome 3: Pain

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Analysis 2.1

Comparison 2: Sclerotherapy (polidocanol) versus sclerotherapy (any sclerosing agent), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 2.2

Comparison 2: Sclerotherapy (polidocanol) versus sclerotherapy (any sclerosing agent), Outcome 2: Adverse events

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Analysis 2.3

Comparison 2: Sclerotherapy (polidocanol) versus sclerotherapy (any sclerosing agent), Outcome 3: Pain

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Analysis 3.1

Comparison 3: Sclerotherapy (STS) versus sclerotherapy (any sclerosing agent), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 3.2

Comparison 3: Sclerotherapy (STS) versus sclerotherapy (any sclerosing agent), Outcome 2: Adverse events

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Analysis 3.3

Comparison 3: Sclerotherapy (STS) versus sclerotherapy (any sclerosing agent), Outcome 3: Pain

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Analysis 4.1

Comparison 4: Sclerotherapy (hypertonic saline) versus sclerotherapy (any sclerosing agent), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 4.2

Comparison 4: Sclerotherapy (hypertonic saline) versus sclerotherapy (any sclerosing agent), Outcome 2: Adverse events

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Analysis 4.3

Comparison 4: Sclerotherapy (hypertonic saline) versus sclerotherapy (any sclerosing agent), Outcome 3: Pain

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Analysis 5.1

Comparison 5: Sclerotherapy (chromated glycerin) versus sclerotherapy (any sclerosing agent), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 5.2

Comparison 5: Sclerotherapy (chromated glycerin) versus sclerotherapy (any sclerosing agent), Outcome 2: Adverse events

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Analysis 5.3

Comparison 5: Sclerotherapy (chromated glycerin) versus sclerotherapy (any sclerosing agent), Outcome 3: Pain

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Analysis 6.1

Comparison 6: Foam versus sclerotherapy (any sclerosing agent), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 6.2

Comparison 6: Foam versus sclerotherapy (any sclerosing agent), Outcome 2: Adverse events

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Analysis 6.3

Comparison 6: Foam versus sclerotherapy (any sclerosing agent), Outcome 3: Pain

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Analysis 7.1

Comparison 7: Laser versus sclerotherapy (any sclerosing agent), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 7.2

Comparison 7: Laser versus sclerotherapy (any sclerosing agent), Outcome 2: Adverse events

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Analysis 7.3

Comparison 7: Laser versus sclerotherapy (any sclerosing agent), Outcome 3: Pain

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Analysis 8.1

Comparison 8: Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 8.2

Comparison 8: Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol), Outcome 2: Adverse events

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Analysis 8.3

Comparison 8: Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol), Outcome 3: Pain

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Analysis 9.1

Comparison 9: Sclerotherapy (polidocanol plus glucose) versus sclerotherapy (glucose), Outcome 1: Resolution or improvement of telangiectasias

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Analysis 9.2

Comparison 9: Sclerotherapy (polidocanol plus glucose) versus sclerotherapy (glucose), Outcome 2: Adverse events

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Analysis 9.3

Comparison 9: Sclerotherapy (polidocanol plus glucose) versus sclerotherapy (glucose), Outcome 3: Pain

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Analysis 10.1

Comparison 10: Sclerotherapy plus compression versus sclerotherapy alone, Outcome 1: Resolution or improvement of telangiectasias

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Analysis 10.2

Comparison 10: Sclerotherapy plus compression versus sclerotherapy alone, Outcome 2: Adverse events

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Analysis 10.3

Comparison 10: Sclerotherapy plus compression versus sclerotherapy alone, Outcome 3: Quality of life

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with placebo	Risk with sclerotherapy	Relative effect (95% CI)	№ of participants/procedures* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 11.88 (4.54 to 31.09)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 12 weeks)	Study population		RR 4.06 (1.28 to 12.84)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 12 weeks)	17 per 1000	68 per 1000 (22 to 216)	RR 4.06 (1.28 to 12.84)	528 (3 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
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
^* Three studies used participants as the unit of analysis and one study used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level due to high clinical heterogeneity of the included studies. ^bWe downgraded by one level due to high clinical heterogeneity of the included studies and wide CI of the included studies (imprecision). ^c We downgraded by two levels due to high clinical heterogeneity of the included studies and only one included study with few participants.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosant agent)	Risk with sclerotherapy (polidocanol)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.94 (0.62 to 1.43)	819 (6 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 16 weeks)	Study population		RR 0.82 (0.52 to 1.27)	859 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 16 weeks)	144 per 1000	118 per 1000 (75 to 183)	RR 0.82 (0.52 to 1.27)	859 (7 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
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
^* Three studies used participants as the unit of analysis and four studies used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level due to wide CIs.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosant)	Risk with sclerotherapy (STS)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 1.71 (1.10 to 2.64)	478 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 24 weeks)	Study population		RR 2.10 (1.14 to 3.85)	323 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 4 ‐ 24 weeks)	82 per 1000	173 per 1000 (94 to 318)	RR 2.10 (1.14 to 3.85)	323 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 1 day)	Study population		RR 1.49 (0.99 to 2.25)	409 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 1 day)	275 per 1000	410 per 1000 (273 to 619)	RR 1.49 (0.99 to 2.25)	409 (4 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
^* Two studies used participants as the unit of analysis and four studies used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level due to wide CIs and small number of participants.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosant)	Risk with sclerotherapy (hypertonic saline)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.74 (0.59 to 0.93)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 8 ‐ 12 weeks)	Study population		RR 0.89 (0.58 to 1.36)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
Adverse events ‐ matting (follow‐up: 8 ‐ 12 weeks)	215 per 1000	192 per 1000 (125 to 293)	RR 0.89 (0.58 to 1.36)	288 (2 RCTs)	⊕⊕⊕⊝ MODERATE^b	‐
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
^* All studies used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by one level because of high risk of other bias in the included studies. ^bWe downgraded by one level because of wide CIs. ^cWe downgraded by one level because of clinical heterogeneity between included studies.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosing agent)	Risk with sclerotherapy (chromated glycerin)	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.49 (0.09 to 2.50)	125 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 5 ‐ 24 weeks)	Study population		RR 0.31 (0.01 to 7.53)	99 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 5 ‐ 24 weeks)	21 per 1000	6 per 1000 (0 to 157)	RR 0.31 (0.01 to 7.53)	99 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
Pain (follow‐up: 1 day)	Study population		RR 1.50 (0.30 to 7.55)	26 (1 RCT)	⊕⊕⊝⊝ LOW^a	‐
Pain (follow‐up: 1 day)	154 per 1000	231 per 1000 (46 to 1000)	RR 1.50 (0.30 to 7.55)	26 (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
^* One study used participants as the unit of analysis and one study used the number of procedures as the unit of analysis for each comparison. ^a We downgraded by two levels due to few included studies and participants.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy (any sclerosing agent)	Risk with foam	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 2.12 (0.44 to 10.23)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow up: 5 ‐ 10 weeks)	Study population		RR 6.12 (1.04 to 35.98)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow up: 5 ‐ 10 weeks)	9 per 1000	53 per 1000 (9 to 310)	RR 6.12 (1.04 to 35.98)	187 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
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
^* One study used participants as the unit of analysis and one study used the number of procedures as the unit of analysis for each comparison. ^aWe downgraded by two levels due to wide CIs and few participants in the included studies.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy	Risk with laser	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.57 (0.40 to 0.80)	262 (4 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 ‐ 24 weeks)	Study population		RR 1.00 (0.46 to 2.19)	162 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 ‐ 24 weeks)	123 per 1000	123 per 1000 (57 to 270)	RR 1.00 (0.46 to 2.19)	162 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 1 day)	Study population		‐	100 (2 RCTs)	⊕⊝⊝⊝ LOW^b	We were not able to pool the data due to high heterogeneity
Pain (follow‐up: 1 day)	See comment	‐	‐	100 (2 RCTs)	⊕⊝⊝⊝ LOW^b	We were not able to pool the data due to high heterogeneity
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
^* Two studies used participants as the unit of analysis and three studies used the number of procedures as the unit of analysis for each comparison ^aWe downgraded by one level due to wide CIs. ^bWe downgraded by two levels because of few included participants.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy	Risk with laser plus sclerotherapy	Relative effect (95% CI)	№ of participants/procedures^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.83 (0.35 to 1.99)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 12 ‐ 16 weeks)	Study population		RR 0.83 (0.21 to 3.28)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Adverse events ‐ matting (follow‐up: 12 ‐ 16 weeks)	18 per 1000	15 per 1000 (4 to 60)	RR 0.83 (0.21 to 3.28)	656 (2 RCTs)	⊕⊕⊝⊝ LOW^a	‐
Pain (follow‐up: 1 day)	Study population		RR 2.44 (1.69 to 3.55)	596 (1 RCT)	⊕⊕⊝⊝ LOW^b	‐
Pain (follow‐up: 1 day)	266 per 1000	649 per 1000 (449 to 944)	RR 2.44 (1.69 to 3.55)	596 (1 RCT)	⊕⊕⊝⊝ LOW^b	‐
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
^* All studies used participants as the unit of analysis. ^aWe downgraded by two levels because of clinical heterogeneity in the included studies and the fact that the two studies were conducted by the same group of investigators. ^bWe downgraded by two levels due to having one included study.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	No of Participants^* (studies)	Certainty of the evidence (GRADE)	Comments
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	Risk with hypertonic glucose	Risk with hypertonic glucose plus POL	Relative effect (95% CI)	No of Participants^* (studies)	Certainty of the evidence (GRADE)	Comments
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)	RR 0.79 (0.62 to 1.01)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 weeks)	Study population		RR 0.78 (0.51 to 1.20)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 16 weeks)	351 per 1000	273 per 1000 (179 to 421)	RR 0.78 (0.51 to 1.20)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 16 weeks)	Study population		RR 1.02 (0.83 to 1.24)	191 (2 RCTs)	⊕⊕⊕⊝ MODERATE^a	‐
Pain (follow‐up: 16 weeks)	443 per 1000	442 per 1000 (359 to 537)	RR 1.02 (0.83 to 1.24)	191 (2 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; 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
^* All studies used participants as the unit of analysis. ^aWe downgraded one level because of few participants in included studies.

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

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

Outcomes	*Anticipated absolute effects^ (95% CI)**		Relative effect (95% CI)	№ of participants (studies)^*	Certainty of the evidence (GRADE)	Comments
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	Risk with sclerotherapy	Risk with sclerotherapy plus compression	Relative effect (95% CI)	№ of participants (studies)^*	Certainty of the evidence (GRADE)	Comments
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)	RR 0.93 (0.41 to 2.07)	196 (2 studies)	⊕⊕⊕⊝ MODERATE^a	‐
Adverse events ‐ matting (follow‐up: 8 weeks)	Study population		RR 1.84 (0.17 to 19.62)	96 (1 study)	⊕⊕⊝⊝ LOW^b	‐
Adverse events ‐ matting (follow‐up: 8 weeks)	22 per 1000	40 per 1000 (4 to 427)	RR 1.84 (0.17 to 19.62)	96 (1 study)	⊕⊕⊝⊝ LOW^b	‐
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
^*All studies used participants as the unit of analysis. ^aWe downgraded one level because of few participants in included studies. ^bWe downgraded two levels because of few participants and only one included study.

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

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Comparison 1. Sclerotherapy (any sclerosing agent) versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Resolution or improvement of telangiectasias Show forest plot	4	613	Std. Mean Difference (IV, Random, 95% CI)	3.08 [2.68, 3.48]

1.2 Adverse events Show forest plot	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 Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 1. Sclerotherapy (any sclerosing agent) versus placebo

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Comparison 2. Sclerotherapy (polidocanol) versus sclerotherapy (any sclerosing agent)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Resolution or improvement of telangiectasias Show forest plot	7	852	Std. Mean Difference (IV, Random, 95% CI)	0.01 [‐0.13, 0.14]

2.2 Adverse events Show forest plot	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 Show forest plot	5	480	Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.44, ‐0.08]

Comparison 2. Sclerotherapy (polidocanol) versus sclerotherapy (any sclerosing agent)

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Comparison 3. Sclerotherapy (STS) versus sclerotherapy (any sclerosing agent)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Resolution or improvement of telangiectasias Show forest plot	4	473	Std. Mean Difference (IV, Random, 95% CI)	‐0.07 [‐0.25, 0.11]

3.2 Adverse events Show forest plot	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 Show forest plot	4	409	Risk Ratio (M‐H, Random, 95% CI)	1.49 [0.99, 2.25]

Comparison 3. Sclerotherapy (STS) versus sclerotherapy (any sclerosing agent)

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Comparison 4. Sclerotherapy (hypertonic saline) versus sclerotherapy (any sclerosing agent)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Resolution or improvement of telangiectasias Show forest plot	3	348	Std. Mean Difference (IV, Random, 95% CI)	0.01 [‐0.20, 0.22]

4.2 Adverse events Show forest plot	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 Show forest plot	3	348	Std. Mean Difference (IV, Random, 95% CI)	6.22 [5.70, 6.73]

Comparison 4. Sclerotherapy (hypertonic saline) versus sclerotherapy (any sclerosing agent)

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Comparison 5. Sclerotherapy (chromated glycerin) versus sclerotherapy (any sclerosing agent)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Resolution or improvement of telangiectasias Show forest plot	2	125	Std. Mean Difference (IV, Random, 95% CI)	0.45 [‐0.11, 1.02]

5.2 Adverse events Show forest plot	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 Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Comparison 5. Sclerotherapy (chromated glycerin) versus sclerotherapy (any sclerosing agent)

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Comparison 6. Foam versus sclerotherapy (any sclerosing agent)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Resolution or improvement of telangiectasias Show forest plot	2	187	Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.26, 0.34]

6.2 Adverse events Show forest plot	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 Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 6. Foam versus sclerotherapy (any sclerosing agent)

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Comparison 7. Laser versus sclerotherapy (any sclerosing agent)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Resolution or improvement of telangiectasias Show forest plot	5	593	Std. Mean Difference (IV, Random, 95% CI)	‐0.09 [‐0.25, 0.07]

7.2 Adverse events Show forest plot	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 Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only

Comparison 7. Laser versus sclerotherapy (any sclerosing agent)

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Comparison 8. Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
8.1 Resolution or improvement of telangiectasias Show forest plot	2	710	Std. Mean Difference (IV, Random, 95% CI)	5.68 [5.14, 6.23]

8.2 Adverse events Show forest plot	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 Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

Comparison 8. Laser plus sclerotherapy (polidocanol) versus sclerotherapy (polidocanol)

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Comparison 9. Sclerotherapy (polidocanol plus glucose) versus sclerotherapy (glucose)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
9.1 Resolution or improvement of telangiectasias Show forest plot	2	191	Std. Mean Difference (IV, Random, 95% CI)	0.79 [0.50, 1.09]

9.2 Adverse events Show forest plot	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 Show forest plot	2	191	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.83, 1.24]

Comparison 9. Sclerotherapy (polidocanol plus glucose) versus sclerotherapy (glucose)

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Comparison 10. Sclerotherapy plus compression versus sclerotherapy alone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
10.1 Resolution or improvement of telangiectasias Show forest plot	2	196	Std. Mean Difference (IV, Random, 95% CI)	0.09 [‐0.19, 0.37]

10.2 Adverse events Show forest plot	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 Show forest plot	1		Std. Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 10. Sclerotherapy plus compression versus sclerotherapy alone

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Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

PICO

PICO

Population

Intervention

Comparison

Outcome

Ringkasan bahasa mudah

Rawatan untuk telangiektasias dan vena retikular

Resumen visual

Authors' conclusions

Implications for practice

Implications for research

Summary of findings

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

Included studies

Type of study

Setting

Unit of analysis

Study participants

Interventions

Outcomes

Excluded studies

Ongoing studies

Risk of bias in included studies

Allocation

Random sequence generation

Allocation concealment

Blinding

Blinding of participants and personnel

Blinding of outcome assessment

Incomplete outcome data

Selective reporting

Other potential sources of bias

Effects of interventions

Sclerotherapy (any sclerosing agent) versus placebo

Resolution or improvement of telangiectasias

Adverse events

Pain during procedure and post‐procedure

Foam (STS plus air) versus foam (STS plus CO₂)