Punctal plugs compared with no punctal plugs for dry eye syndrome

Patient or population: adults with dry eye syndrome

Settings: eye clinics

Intervention: silicone or collagen punctal plugs

Comparison: no punctal plugs (observation or sham treatment)

Symptomatic improvement

Follow‐up: long‐term*

A lower score favors punctal plugs

—

89

(2 RCT)

⊕⊝⊝⊝
Very low^a,b

Mansour 2007 reported little or no difference in Ocular and Oral Symptoms score, which ranged from 0 to 10 points (MD ‐0.46 points, 95% CI ‐1.24 to 0.32; eyes = 26).

Nava‐Castaneda 2003 reported a slight decrease in symptom score, assumed to range from 0 to 105 points, but it does not seem to be clinically important (MD ‐2.62 points, 95% CI ‐3.32 to ‐1.93; eyes = 61).

Yung 2012 reported little or no difference in dry eye symptom score, ranging from 0 to 3 points (MD ‐0.75 points, 95% CI ‐1.53 to 0.02; eyes = 28)

Ocular surface staining

Follow‐up: long‐term*

A higher value is less advantageous

Both Rose Bengal and fluorescein staining scores ranged from 0 to 4, where 0 represented no staining and 4 represented heavy staining

—

61

(1 RCT)

⊕⊕⊝⊝
Low^c,d

—

Aqueous tear production

Follow‐up: long‐term*

A higher value is more advantageous

—

28

(1 RCT)

⊕⊕⊝⊝
Low^c,d

Yung 2012 did not provide quantitative data, but reported that "Schirmer values tended to increase in the plug group after plug insertion; however, the changes did not reach significance"

Tear film stability

Follow‐up: 6 months

A higher value is more advantageous

—

28

(1 RCT)

⊕⊕⊝⊝
Low^a,b

—

Artificial tear use

Follow‐up: long‐term*

Fewer applications favors punctal plugs

—

61

(1 RCT)

⊕⊕⊝⊝
Low^e

—

Adverse events

Follow‐up: end of study

—

146
(4 RCT)

⊕⊝⊝⊝
Very low^f,g

Slusser 1998: all adverse events occurred in the punctal plug group, reported 23/28 participants had epiphora, 3/28 participants reported itching in area of plug placement, 1/28 participants had tenderness and swelling of lids with mucous discharge.

Spontaneous plug loss occurred in 6/20 eyes with silicone punctal plugs in the Mansour 2007.

One or 31 participants receiving collagen and silicone punctal plugs experienced epiphora in the Nava‐Castaneda 2003 study.

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; SMD: standardized mean difference; RCT: randomized controlled trial.

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.

Punctal plugs compared with cyclosporine for dry eye syndrome

Patient or population: adults with dry eye syndrome

Settings: eye clinics

Intervention: punctal plugs

Comparison: cyclosporine

Symptomatic improvement

Ocular surface staining

Follow‐up: 6 months

Any value greater than zero is abnormal

Range: 0 to 4 points; 0 = no staining, 1 = staining of the nasal conjunctiva only, 2 = staining of both the nasal and temporal conjunctiva, 3 = peripheral corneal staining, 4 = central corneal staining

20

(1 RCT)

⊕⊝⊝⊝
Very low^a,b

The study investigators of Roberts 2007 stated: "there was greater improvement in conjunctival staining with cyclosporine or the combination than with plugs alone." It was unclear whether Rose Bengal or fluorescein staining was used. Also,

the study investigators did not specify the time point and so we assumed that their statement applies for 1, 3, and 6 months follow‐up.

Aqueous tear production

Follow‐up: 6 months

A higher value is more advantageous

20
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

The study investigators of Roberts 2007 stated: "There was a greater increase in Schirmer score with plugs, either alone or in combination with cyclosporine." The study investigators did not specify the for which time point and so we assumed that their statement applies for 1, 3, and 6 months follow‐up.

Tear film stability

Follow‐up: 6 months

Artificial tear use

Follow‐up: 6 months

range: 1‐5 applications

Fewer applications favors punctal plugs

20
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

The study investigators of Roberts 2007 stated: "decreased frequency of artificial tears was greatest for combination therapy and least for punctal plugs." The study investigators did not specify the for which time point and so we assumed that their statement applies for 1, 3, and 6 months follow‐up.

Adverse events

Follow‐up: end of study

22
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

Roberts 2007 reported 1/11 participants experienced plug displacement in the plug group, while 1/11 participants experienced a burning sensation in the cyclosporine group.

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; RCT: randomized controlled trial.

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.

Punctal plugs compared with oral pilocarpine for dry eye syndrome

Patient or population: adults with dry eye syndrome

Settings: eye clinics

Intervention: punctal plugs

Comparison: oral pilocarpine

Symptomatic improvement

Follow‐up: 3 months

The study investigators defined improvements in subjective ocular symptoms as an improvement of >55 mm for responses to the eye questionnaire on a 100 mm visual analog scale.

A RR less than one favors punctal plugs.

RR 0.69

(0.49 to 0.95)

55
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

‐

Ocular surface staining

Follow‐up: 3 months

A higher value is less advantageous

Range: van Bijsterveld schema, which is on a scale of 0 to 9 points

—

55
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

—

55
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Aqueous tear production

Follow‐up: 3 months

A higher value more advantageous

—

55
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

—

55
(1 RCT)

—

Tear film stability

Artificial tear use

Adverse events

Follow‐up: 3 months

—

55
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

Tsifetaki 2003 reported: "commonly reported adverse events were headache, increased sweating,nausea, and vomiting in the pilocarpine group, while 1 patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study." pg 1204

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; RCT: randomized controlled trial

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.

Punctal plugs compared with artificial tears for dry eye syndrome

Patient or population: adults with dry eye syndrome

Settings: eye clinics

Intervention: punctal plugs

Comparison: artificial tears

Symptomatic improvement

Follow‐up: 3 months

The study investigators defined improvements in subjective ocular symptoms as an improvement of >55 mm for responses to the eye questionnaire on a 100 mm visual analog scale.

A RR greater than one favors punctal plugs.

Both studies used different symptomatic improvement score; one study used the Ocular Surface Disease Index that ranged from 0 points = never to 4 points = all the time. The second study use the sum of scores for dryness, foreign body sensation, and visual fatigue; each score had a different range, but a higher score corresponded to more symptoms.

RR 2.29

(1.2 to 4.38)

54

(1 RCT)

⊕⊝⊝⊝
Very low^a,b,c

—

—

130

(2 RCTs)

—

Ocular surface staining

Follow‐up: 3 months

Range: 0 = absent; 1 = trace; 2 = mild; 3 = moderate; 4 =

severe

A higher value is worse

—

55
(1 RCT)

⊕⊕⊝⊝
Low^d

—

—

55
(1 RCT)

—

Aqueous tear production

Follow‐up: long‐term*

A higher value is more advantageous

—

54
(1 RCT)

⊕⊕⊝⊝
Low^c,e

—

—

54
(1 RCT)

—

—

130

(2 RCTs)

—

Tear film stability

Follow‐up: long‐term*

A higher value is more advantageous

—

130
(2 RCT)

⊕⊕⊕⊝
Moderate^c

—

Artificial tear use

Adverse events (punctate epithelial keratopathy)

Follow‐up: end of study

RR 1.33 (0.57 to 3.12)

54
(1 RCT)

⊕⊕⊝⊝
Low^a,c

Tsifetaki 2003 reported: "four patients had mild headache, of whom three also presented with nausea, vomiting, and sweating" (p 1205) and "one patient in the inferior puncta occlusion group had blepharitis and was withdrawn from the study" (p 1204)

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; RCT: randomized controlled trial

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.

Punctal plugs occluded in the upper puncta compared with the lower puncta for dry eye syndrome

Patient or population: adults with dry eye syndrome

Settings: eye clinics

Intervention: punctal plugs occluded in the upper puncta

Comparison: punctal plugs occluded in the lower puncta

Symptomatic improvement

Follow‐up: long‐term*

Ocular surface staining

Follow‐up: long‐term*

Aqueous tear production

Follow‐up: long‐term*

Tear film stability

Follow‐up: long‐term*

Artificial tear use

Adverse events

See comments

40
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

Chen 2010 reported "no complication was observed in dry eye patients or control subjects during the period of this study." It is unclear which complications were collected.

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; RCT: randomized controlled trial

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.

Acrylic punctal plugs compared with silicone punctal plugs for dry eye syndrome

Patient or population: mostly women with dry eye syndrome

Settings: eye clinics

Intervention: acrylic punctal plugs

Comparison: silicone punctal plugs

Symptomatic improvement

Follow‐up: 11 weeks

Range: 0 to 70 points

A visual analog scales 10 cm in length for seven symptoms: dryness, grittiness, foreign body sensation, pain, stinging, burning, and itching was used.

A lower score favors acrylic punctal plugs

—

36
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Ocular surface staining

Follow‐up: 11 weeks

A higher value is less advantageous

Range: 0 to 3 points

—

36
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

—

—

Aqueous tear production

Follow‐up: 11 weeks

A higher value is more advantageous

—

36
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

Authors did not report the time interval in which the Schirmer's test 1 without anesthesia was performed. We assumed it was done over 5 minutes.

Tear film stability

Follow‐up: 11 weeks

A higher value is more advantageous

—

36
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Artificial tear use

Follow‐up: 11 weeks

Range: 1‐5 applications

Fewer applications favors punctal plugs

—

36
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Adverse events

Follow‐up: 11 weeks

—

36
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

1 acrylic punctal plug participant experienced epiphora, 1 silicone punctal plug participant experienced intermittent ocular irritation, and 2 silicone and 1 acrylic punctal plug participants experienced temporary foreign body sensation.

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; RCT: randomized controlled trial.

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.

Intracanalicular punctal plugs compared with silicone punctal plugs for dry eye syndrome

Patient or population: adults with dry eye syndrome

Settings: eye clinics

Intervention: intracanalicular punctal plugs

Comparison: silicone punctal plugs

Symptomatic improvement

Follow‐up: 3 months

Subjective dry eye symptoms for each eye was reported; investigators measured soreness, scratching, grittiness, dryness and/or burning using a 100 mm visual analog scale (VAS; 0 mm = no symptoms, 100 mm = maximum intensity)

—

57
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Ocular surface staining

Follow‐up: 3 months

A higher value is less advantageous

Range: 0 to 3 points; 0 = no staining and 3 = most intense staining

—

57
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

—

57
(1 RCT)

—

Aqueous tear production

Follow‐up: 3 months

Tear film stability

Follow‐up: 3 months

Artificial tear use

Follow‐up: 3 months

Fewer applications favors intracanalicular plugs

—

57
(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Adverse events

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; RCT: randomized controlled trial

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.

Collagen punctal plugs compared with silicone punctal plugs for dry eye syndrome

Patient or population: adults with dry eye syndrome

Settings: eye clinics

Intervention: collagen punctal plugs

Comparison: silicone punctal plugs

Symptomatic improvement

Follow‐up: 3 months

The Canadian Dry Eye Assessment range from 0 to 48 points; where less than 5 points was normal, 5 to 15 points was mild, 20 to 25 points was moderate, 30 to 48 points was severe.

—

50

(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Ocular surface staining

Follow‐up: 3 months

Range: 0 to 15 points

A higher value is less advantageous

—

50

(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Aqueous tear production

Follow‐up: 3 months

A higher value is more advantageous

—

50

(1 RCT)

⊕⊝⊝⊝
Very low^a,b

Authors did not report the time interval in which the Schirmer's test 1 without anesthesia was performed. We assumed it was done over 5 minutes.

Tear film stability

Follow‐up: 3 months

A higher value is more advantageous

—

50

(1 RCT)

⊕⊝⊝⊝
Very low^a,b

—

Artificial tear use

Follow‐up: 3 months

Fewer applications favors collagen punctal plugs

—

50

(1 RCT)

⊕⊕⊝⊝
Low^a

—

Adverse events

Follow‐up: end of study

See comments

98

(2 RCT)

⊕⊝⊝⊝
Very low^a,b

Both studies reported that none of the participants developed adverse events or complications related to punctal plugs.

*The basis for the assumed risk is the control group risk across studies. The corresponding risk (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; RR: risk ratio; RCT: randomized controlled trial.

GRADE Working Group grades of evidence
High‐certainty: further research is very unlikely to change our confidence in the estimate of effect.
Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low‐certainty: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low‐certainty: we are very uncertain about the estimate.