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Cochrane Database of Systematic Reviews

Fármacos perioperatorios para la prevención del aumento temporal de la presión intraocular después de la trabeculoplastia con láser

Information

DOI:
https://doi.org/10.1002/14651858.CD010746.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 23 February 2017see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Eyes and Vision Group

Copyright:
  1. Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Linda Zhang

    Correspondence to: The Eye Center, Warren, USA

    [email protected]

  • Jennifer S Weizer

    Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, USA

  • David C Musch

    Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, USA

Contributions of authors

The protocol for this review was written by LZ with significant contributions from JW and DM.
Screening and data extraction: LZ and JW with assistance from CEV staff Elizabeth Clearfield (EC), Sueko Ng, and Nan Zhang.
Data checking and entering: EC.
Data reviewed: LZ.
Writing: LZ and EC with contributions from JW and DM.

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • Grant 1 U01 EY020522, National Eye Institute, National Institutes of Health, USA.

    Funding for methodological support from the Cochrane Eyes and Vision US Project

  • National Institute for Health Research (NIHR), UK.

    • Richard Wormald, Co‐ordinating Editor for Cochrane Eyes and Vision (CEV) acknowledges financial support for his CEV research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.

    • The NIHR also funds the CEV Editorial Base in London.

    The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the Department of Health.

Declarations of interest

LZ none known.
JW none known.
DM none known.

Acknowledgements

We acknowledge the Cochrane Eyes and Vision (CEV) US Project for providing methodological support and for developing and conducting the search strategies. We also thank Barbara Hawkins, Stefano Miglior, and Augusto Azuara‐Blanco for comments to the review drafts.

Version history

Published

Title

Stage

Authors

Version

2017 Feb 23

Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty

Review

Linda Zhang, Jennifer S Weizer, David C Musch

https://doi.org/10.1002/14651858.CD010746.pub2

2013 Sep 11

Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty

Protocol

Linda Zhang, Jennifer S Weizer, David C Musch

https://doi.org/10.1002/14651858.CD010746

Differences between protocol and review

We added the methods for the 'Summary of findings' tables and GRADE assessment that were not included in the original protocol. We were unable to use some methods and perform some analyses we had outlined in the protocol (Zhang 2013). For example, we had planned to conduct sensitivity analyses to assess the influence of industry‐funded studies, studies with missing data, and studies assessed as having a high risk of selection or attrition bias, but selection and attrition bias were not major concerns among our included studies. We had also planned a sensitivity analysis to remove industry‐funded studies, but the majority of the studies contributing data to our analyses were industry‐funded, and removing them would leave too few data to draw any conclusions.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 2

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

Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
Figures and Tables -
Figure 3

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

Forest plot of comparison: 1 Medication versus placebo (regardless of timing), outcome: 1.4 Intraocular pressure (IOP) increase ≥ 5 mmHg two to 24 hours after laser trabeculoplasty (LTP).
Figures and Tables -
Figure 4

Forest plot of comparison: 1 Medication versus placebo (regardless of timing), outcome: 1.4 Intraocular pressure (IOP) increase ≥ 5 mmHg two to 24 hours after laser trabeculoplasty (LTP).

Forest plot of comparison: 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), outcome: 3.2 Intraocular pressure (IOP) increase of ≥ 5 mmHg two to 24 after laser trabeculoplasty (LTP).
Figures and Tables -
Figure 5

Forest plot of comparison: 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), outcome: 3.2 Intraocular pressure (IOP) increase of ≥ 5 mmHg two to 24 after laser trabeculoplasty (LTP).

Forest plot of comparison: 4 Timing comparison: medication before versus medication after, outcome: 4.1 Intraocular pressure (IOP) increase of ≥ 5 mmHg two to 24 hours after laser trabeculoplasty (LTP).
Figures and Tables -
Figure 6

Forest plot of comparison: 4 Timing comparison: medication before versus medication after, outcome: 4.1 Intraocular pressure (IOP) increase of ≥ 5 mmHg two to 24 hours after laser trabeculoplasty (LTP).

Comparison 1 Medication versus placebo (regardless of timing), Outcome 1 Intraocular pressure (IOP) increase of ≥ 5 mmHg within 2 hours after laser trabeculoplasty (LTP).
Figures and Tables -
Analysis 1.1

Comparison 1 Medication versus placebo (regardless of timing), Outcome 1 Intraocular pressure (IOP) increase of ≥ 5 mmHg within 2 hours after laser trabeculoplasty (LTP).

Comparison 1 Medication versus placebo (regardless of timing), Outcome 2 IOP increase of ≥ 10 mmHg within 2 hours after LTP.
Figures and Tables -
Analysis 1.2

Comparison 1 Medication versus placebo (regardless of timing), Outcome 2 IOP increase of ≥ 10 mmHg within 2 hours after LTP.

Comparison 1 Medication versus placebo (regardless of timing), Outcome 3 Mean change in IOP from pre‐LTP to measurements taken within 2 hours after LTP.
Figures and Tables -
Analysis 1.3

Comparison 1 Medication versus placebo (regardless of timing), Outcome 3 Mean change in IOP from pre‐LTP to measurements taken within 2 hours after LTP.

Comparison 1 Medication versus placebo (regardless of timing), Outcome 4 IOP increase of ≥ 5 mmHg two to 24 hours after LTP.
Figures and Tables -
Analysis 1.4

Comparison 1 Medication versus placebo (regardless of timing), Outcome 4 IOP increase of ≥ 5 mmHg two to 24 hours after LTP.

Comparison 1 Medication versus placebo (regardless of timing), Outcome 5 IOP elevation of ≥ 10 mmHg two to 24 hours after LTP.
Figures and Tables -
Analysis 1.5

Comparison 1 Medication versus placebo (regardless of timing), Outcome 5 IOP elevation of ≥ 10 mmHg two to 24 hours after LTP.

Comparison 1 Medication versus placebo (regardless of timing), Outcome 6 Mean change in IOP from pre‐LTP to measurements two to 24 hours after LTP.
Figures and Tables -
Analysis 1.6

Comparison 1 Medication versus placebo (regardless of timing), Outcome 6 Mean change in IOP from pre‐LTP to measurements two to 24 hours after LTP.

Comparison 2 Medication versus medication: brimonidine versus apraclonidine (regardless of timing), Outcome 1 Intraocular pressure (IOP) increase of ≥ 5 mmHg within 2 hours after laser trabeculoplasty (LTP).
Figures and Tables -
Analysis 2.1

Comparison 2 Medication versus medication: brimonidine versus apraclonidine (regardless of timing), Outcome 1 Intraocular pressure (IOP) increase of ≥ 5 mmHg within 2 hours after laser trabeculoplasty (LTP).

Comparison 2 Medication versus medication: brimonidine versus apraclonidine (regardless of timing), Outcome 2 Mean change in IOP from pre‐LTP to measurements taken within 2 hours after LTP (mmHg).
Figures and Tables -
Analysis 2.2

Comparison 2 Medication versus medication: brimonidine versus apraclonidine (regardless of timing), Outcome 2 Mean change in IOP from pre‐LTP to measurements taken within 2 hours after LTP (mmHg).

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 1 Mean change in intraocular pressure (IOP) from pre‐laser trabeculoplasty (LTP) to measurements taken within 2 hours after LTP (mmHg).
Figures and Tables -
Analysis 3.1

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 1 Mean change in intraocular pressure (IOP) from pre‐laser trabeculoplasty (LTP) to measurements taken within 2 hours after LTP (mmHg).

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 2 IOP increase of ≥ 5 mmHg two to 24 hours after LTP.
Figures and Tables -
Analysis 3.2

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 2 IOP increase of ≥ 5 mmHg two to 24 hours after LTP.

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 3 IOP increase of ≥ 10 mmHg two to 24 hours after LTP.
Figures and Tables -
Analysis 3.3

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 3 IOP increase of ≥ 10 mmHg two to 24 hours after LTP.

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 4 Mean change in IOP from pre‐LTP to measurements taken two to 24 hours after LTP (mmHg).
Figures and Tables -
Analysis 3.4

Comparison 3 Medication versus medication: apraclonidine versus pilocarpine (regardless of timing), Outcome 4 Mean change in IOP from pre‐LTP to measurements taken two to 24 hours after LTP (mmHg).

Comparison 4 Timing comparison: medication before versus medication after, Outcome 1 Intraocular pressure (IOP) increase of ≥ 5 mmHg two to 24 hours after laser trabeculoplasty (LTP).
Figures and Tables -
Analysis 4.1

Comparison 4 Timing comparison: medication before versus medication after, Outcome 1 Intraocular pressure (IOP) increase of ≥ 5 mmHg two to 24 hours after laser trabeculoplasty (LTP).

Comparison 4 Timing comparison: medication before versus medication after, Outcome 2 IOP increase of ≥ 10 mmHg two to 24 hours after LTP.
Figures and Tables -
Analysis 4.2

Comparison 4 Timing comparison: medication before versus medication after, Outcome 2 IOP increase of ≥ 10 mmHg two to 24 hours after LTP.

Comparison 4 Timing comparison: medication before versus medication after, Outcome 3 Mean change in IOP from pre‐LTP to measurements taken more than 2 hours but within 24 hours after LTP (mmHg).
Figures and Tables -
Analysis 4.3

Comparison 4 Timing comparison: medication before versus medication after, Outcome 3 Mean change in IOP from pre‐LTP to measurements taken more than 2 hours but within 24 hours after LTP (mmHg).

Comparison 5 Adverse events, Outcome 1 Conjunctival blanching (brimonidine vs placebo).
Figures and Tables -
Analysis 5.1

Comparison 5 Adverse events, Outcome 1 Conjunctival blanching (brimonidine vs placebo).

Summary of findings for the main comparison. Medication compared with placebo for preventing temporarily increased IOP after laser trabeculoplasty

Medication compared with placebo for preventing temporarily increased IOP after LTP

Participant or population: people with glaucoma receiving LTP

Intervention: IOP‐lowering medication (apraclonidine, acetazolamide, brimonidine, pilocarpine)

Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Medication

IOP increase of ≥ 5 mmHg

within 2 hours

See comment

273
(2 RCTs)

⊕⊕⊝⊝1,2
Low

Medications in this comparison were apraclonidine and brimonidine. 2 studies reported on this outcome and 1 favored the alpha‐2 agonists while the other favored placebo. Due to significant statistical heterogeneity (I2 = 70%), we did not perform a meta‐analysis.

IOP increase of ≥ 10 mmHg

within 2 hours

195 per 1000

10 per 1000
(2 to 39)

RR 0.05 (0.01 to 0.20)

446
(4 RCTs)

⊕⊕⊕⊝1
Moderate

Medications in this comparison were acetazolamide, apraclonidine, and brimonidine.

Mean change in IOP from pre‐LTP

within 2 hours

The mean change in IOP ranged across control groups from0.4 mmHg to 4.40 mmHg, for 3 included studies

The mean change in IOP in the intervention groups was 7.43 mmHg lower
(10.60 lower to 4.27 lower)

151
(4 studies)

⊕⊕⊕⊝1
Moderate

Each of the studies included in this outcome compared apraclonidine vs placebo.

IOP increase of ≥ 5 mmHg

between 2 and 24 hours

280 per 1000

48 per 1000
(25 to 87)

RR 0.17 (0.09 to 0.31)

634
(5 studies)

⊕⊕⊝⊝3

Low

Medications in this comparison were apraclonidine and brimonidine.

IOP increase of ≥ 10 mmHg

between 2 and 24 hours

202 per 1000

44 per 1000
(22 to 85)

RR 0.22 (0.11 to 0.42)

817
(9 studies)

⊕⊝⊝⊝3,4
Very low

Medications in this comparison were apraclonidine, brimonidine, dorozolamide, and pilocarpine.

Mean change in IOP from pre‐LTP

between 2 and 24 hours

The mean change in IOP ranged across control groups from‐2.0 mmHg to 0.63 mmHg, for 3 included studies

The mean change in IOP in the intervention groups was 5.32 mmHg lower
(7.37 lower to 3.28 lower)

151
(4 studies)

⊕⊕⊕⊝1
Moderate

Each of the studies included in this outcome compared apraclonidine vs placebo.

Adverse events ‐ conjunctival blanching

during study period

See comment

319

(2 studies)

⊕⊕⊕⊝1
Moderate

2 studies reported on conjunctival blanching; however, due to significant statistical heterogeneity (I2 = 95%), we did not perform a meta‐analysis. In both studies, conjunctival blanching was reported in more participants in the group that received an alpha‐2 agonist compared with participants who received placebo. 1 other study that reported only the range of participants who had conjunctival blanching also reported that this adverse event was more frequent in the groups receiving brimonidine vs placebo. Other adverse events reported for the comparison of medication vs placebo were lid retraction and conjunctival hyperemia, reported in 1 study each.

*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; IOP: intraocular pressure; LTP: laser trabeculoplasty; RCT: randomized controlled trial; RR: risk ratio.

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.

1 The certainty of the evidence was downgraded due to concerns of risk of bias: masking of outcomes assessors was difficult and in one study, the authors of some studies worked with the company making the study drug.

2 The certainty of the evidence was downgraded due to inconsistency of the outcome measurements in the individual studies: one favored medication and one favored placebo.

3 The certainty of the evidence was downgraded two levels due to concerns of very serious plausible bias: some studies in these analyses had issues with masking of outcomes assessors, high risk of selective reporting, and authors associated with the manufacturer of the study drug.

4 The certainty of the evidence was downgraded due to imprecision: there is a small number of events in the medication groups.

Figures and Tables -
Summary of findings for the main comparison. Medication compared with placebo for preventing temporarily increased IOP after laser trabeculoplasty
Summary of findings 2. Brimonidine compared with apraclonidine for preventing temporarily increased IOP after laser trabeculoplasty

Brimonidine compared with apraclonidine for preventing temporarily increased IOP after LTP

Participant or population: people with glaucoma receiving LTP

Intervention: brimonidine

Comparison: apraclonidine

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Apraclonidine

Brimonidine

IOP increase of ≥ 5 mmHg

within 2 hours

29 per 1000

67 per 1000
(9 to 471)

RR 2.28 (0.32 to 16.03)

71
(2 RCTs)

⊕⊝⊝⊝1,2,3
Very low

1 other study reported this outcome but found that no participants in either study group had an IOP increase of ≥ 5 mmHg. This study was not included in the meta‐analysis.

IOP increase of ≥ 10 mmHg

within 2 hours

See comment

1 study reported that no participants given either medication had an IOP increase of ≥ 10 mmHg. Another study reported that only 1 eye that had received apraclonidine had an IOP spike > 10 mmHg, but this was not statistically significant given the size of the study (RR 0.33, 95% CI 0.02 to 7.32).

Mean change in IOP from pre‐LTP

within 2 hours

The mean change in IOP ranged across control groups from‐4.29 to ‐5.00 mmHg

The mean change in IOP in the intervention groups was 0.69 mmHg lower (2.56 lower to 1.17 higher)

71
(2 RCTs)

⊕⊕⊕⊝3
Moderate

IOP increase of ≥ 5 mmHg

between 2 and 24 hours

This outcome was not reported for this comparison.

IOP increase of ≥ 10 mmHg

between 2 and 24 hours

This outcome was not reported for this comparison.

Mean change in IOP from pre‐LTP

between 2 and 24 hours

See comment

1 study reported that participants randomized to receive brimonidine had a mean (± SD) IOP reduction of 2.6 ± 3.6 mmHg, while participants randomized to receive apraclonidine had a mean IOP reduction of 2.3 ± 3.7 mmHg (MD ‐0.30 mmHg, 95% CI ‐2.41 to 1.81).

Adverse events ‐

during study period

This outcome was not reported for this comparison.

*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; IOP: intraocular pressure; LTP: laser trabeculoplasty; MD: mean difference; RCT: randomized controlled trial; RR: risk ratio; SD: standard deviation.

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.

1 The certainty of the evidence was downgraded two levels due to imprecision: our effect measurement had a very wide confidence interval.

2 The certainty of the evidence was downgraded due to inconsistency: the RRs of the individual trials were very different.

3 The certainty of the evidence was downgraded due to concerns of risk of bias: masking of participants and personnel was unclear, and in one study, both eyes of the participants were included in the study and received different medications but the authors did not report if and how they took into account the interdependability of eyes.

Figures and Tables -
Summary of findings 2. Brimonidine compared with apraclonidine for preventing temporarily increased IOP after laser trabeculoplasty
Summary of findings 3. Apraclonidine compared with pilocarpine for temporarily increased IOP after laser trabeculoplasty

Apraclonidine compared with pilocarpine for temporarily increased IOP after LTP

Participant or population: people with glaucoma receiving LTP

Intervention: apraclonidine

Comparison: pilocarpine

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Pilocarpine

Apraclonidine

IOP increase of ≥ 5 mmHg

within 2 hours

See comment

1 study reported that 8.8% of the apraclonidine group had an increase of ≥ 5 mmHg vs 4.4% of the pilocarpine group. These were not statistically different (RR 2.00, 95% CI 0.71 to 5.67).

IOP increase of ≥ 10 mmHg

within 2 hours

This outcome was not reported for this comparison.

Mean change in IOP from pre‐LTP

within 2 hours

The mean change in IOP was only reported in 1 study: ‐3.6 mmHg. The second study reported only the mean IOP at a time point rather than the mean change

The mean change in IOP in the intervention groups was 0.61 mmHg higher (0.44 lower to 1.66 higher)

277
(2 RCTs)

⊕⊕⊕⊝1
Moderate

IOP increase of ≥ 5 mmHg

between 2 and 24 hours

See comment.

⊕⊕⊝⊝1, 2
Low

2 studies reported on this outcome and 1 favored apraclonidine while the other favored pilocarpine. Due to significant statistical heterogeneity (I2 = 91%), we did not perform a meta‐analysis.

IOP increase of ≥ 10 mmHg

between 2 and 24 hours

13 per 1000

12 per 1000
(2 to 75)

RR 0.87 (0.14 to 5.63)

390
(2 RCTs)

⊕⊕⊝⊝2,3
Low

1 additional study reported on this outcome but found that no participants in either study group had an IOP increase of ≥ 10 mmHg. This study was not included in the meta‐analysis.

Mean change in IOP from pre‐LTP

between 2 and 24 hours

See comment.

277
(2 RCTs)

⊕⊕⊝⊝1, 2
Low

2 studies reported on this outcome and 1 favored apraclonidine while the other favored pilocarpine. Due to significant statistical heterogeneity (I2 = 92%), we did not perform a meta‐analysis.

Adverse events ‐

during study period

This outcome was not reported for this comparison.

*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; IOP: intraocular pressure; LTP: laser trabeculoplasty; RCT: randomized controlled trial; RR: risk ratio.

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.

1 The certainty of the evidence was downgraded due to concerns of plausible bias: one study included in the analyses had issues with masking of their participants due to the nature of the study design, and additionally the authors were employees of the company that manufactured the study drug.

2 The certainty of the evidence was downgraded due to inconsistency: in each outcome analysis, one study favored pilocarpine while the other favored apraclonidine.

3 The certainty of the evidence was downgraded due to imprecision: our effect measurement had a very wide confidence interval.

Figures and Tables -
Summary of findings 3. Apraclonidine compared with pilocarpine for temporarily increased IOP after laser trabeculoplasty
Summary of findings 4. Medication given before LTP compared with the same medication given after LTP for temporarily increased IOP after LTP

Medication given before LTP compared with the same medication given after LTP for temporarily increased IOP after LTP

Participant or population: people with glaucoma receiving LTP

Intervention: medication before LTP

Comparison: medication after LTP

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Certainty of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Medication after LTP

Medication before LTP

IOP increase of ≥ 5 mmHg

within 2 hours

See comment

1 study comparing apraclonidine given before and after surgery reported no participants had an increase of ≥ 5 mmHg. Another study reported that 5.3% of participants given brimonidine before surgery had an IOP increase of ≥ 5 mmHg, compared with 7.5% of participants given brimonidine after surgery (RR 0.70, 95% CI 0.16 to 2.97).

IOP increase of ≥ 10 mmHg

within 2 hours

See comment

1 study comparing apraclonidine given before and after surgery reported no participants had an increase of ≥ 10 mmHg. Another study reported that only 1 study participant had this high of an increase, and they had been randomized to brimonidine before surgery.

Mean change in IOP from pre‐LTP

within 2 hours

See comment

Mean change in IOP from pre‐LTP to measurements taken within 2 hours after LTP was not reported in any study, but 1 study did report the mean IOP for the 2 study arms within 2 hours and it was not statistically different between the 2 groups.

IOP increase of ≥ 5 mmHg

between 2 and 24 hours

38 per 1000

31 per 1000
(9 to 100)

RR 0.82 (0.25 to 2.63)

319
(4 RCTs)

⊕⊕⊕⊝1
Moderate

IOP increase of ≥ 10 mmHg

between 2 and 24 hours

6 per 1000

10 per 1000
(1 to 79)

RR 1.55 (0.19 to 12.43)

319
(4 RCTs)

⊕⊝⊝⊝1,2
Very low

Mean change in IOP from pre‐LTP

between 2 and 24 hours

The mean change in IOP was only reported in 1 study: ‐3.4 mmHg. The other 2 studies reported only the mean IOP at a time point rather than the mean change: range was13.0 mmHg to 18.6 mmHg

The mean change in IOP in the intervention groups was 1.07 mmHg lower (2.51 lower to 0.37 higher)

198
(3 RCTs)

⊕⊕⊕⊝3
Moderate

Adverse events ‐

during study period

This outcome was not reported for this comparison.

*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; IOP: intraocular pressure; LTP: laser trabeculoplasty; RCT: randomized controlled trial; RR: risk ratio.

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.

1 The certainty of the evidence was downgraded due to concerns of plausible bias: masking of outcomes assessors was difficult and the authors of two studies work with the company making the study drug; one study had a high risk of selective reporting bias.

2 The certainty of the evidence was downgraded two levels due to imprecision: the included studies for which data were available had very wide confidence intervals.

3 The certainty of the evidence was downgraded due to inconsistency: of the three included studies, two favored medication given before surgery, and the other favored medication given after surgery.

Figures and Tables -
Summary of findings 4. Medication given before LTP compared with the same medication given after LTP for temporarily increased IOP after LTP
Table 1. Study Comparison

Study ID

Types of participants

Number of treatment groups

Type of trabeculoplasty

Degree of laser

Comparison (baseline IOP in mmHg)

Barnebey 1993

Uncontrolled glaucoma

4

ALT

360

Brimonidine before and after

vs

brimonidine before and vehicle after

vs

vehicle before and brimonidine after

vs

vehicle before and after

(individual baseline IOPs not reported; range 23.4 ± 0.6 to 24.3 ± 0.7)

Barnes 1999

POAG, pigmentary glaucoma, pseudoexfoliation syndrome, or ocular hypertension

2

ALT

360

Brimonidine (19.6 ± 4.5)

vs

apraclonidine (20.5 ± 4.6)

Birt 1995

POAG

3

ALT

180

Apraclonidine before and after (22.2 ± 3.6)

vs

apraclonidine before (23.9 ± 5.3)

vs

apraclonidine after (22.1 ± 3.2)

Brown 1988

Inadequately controlled IOP despite maximum‐tolerated medical therapy

2

ALT

360

Apraclonidine before and after

vs

placebo before and after

(IOPs not available)

Carassa 1992

Advanced glaucoma on maximal tolerated medical therapy with inadequate IOP control

2

ALT

360

Apraclonidine before and after (19.20 ± 5.95)

vs

placebo before and after (19.80 ± 5.23)

Chevrier 1999

Candidates for ALT, peripheral iridectomy, or posterior capsulotomy

2

ALT

180

Brimonidine before (20.3 ± 6)

vs

apraclonidine before (20.0 ± 5.1)

*the reported IOPs included participants who received other types of glaucoma surgery besides ALT

Dapling 1994

OAG

3 (1 combination group not of interest in this study)

ALT

180

Apraclonidine before and after

vs

pilocarpine after

("all eyes had...an IOP greater than 21mmHg")

David 1993

Participants undergoing ALT

4

ALT

360

Brimonidine before and after (23.3)

vs

brimonidine before, placebo after (23.9)

vs

placebo before, brimonidine after (24.1)

vs

placebo before and after (24.0)

Donnelly 2006

POAG

2 (opposite eyes)

SLT

360

Brimonidine before

vs

apraclonidine after

(right eyes: 18, left eyes: 18.4)

Elsas 1991

Exfoliative glaucoma and simple glaucoma

2

ALT

360

Pilocarpine before (34.9 ± 8.1)

vs

no treatment (33.3 ± 5.6)

Hartenbaum 1999

OAG requiring ALT

2

ALT

180

Dorzolamide before and after (18.3 ± 0.57)

vs

placebo before and after (19.6 ± 0.72)

Holmwood 1992

OAG

2

ALT

360

Apraclonidine before and after (22.6 ± 0.9)

vs

apraclonidine after (22.6 ± 0.6)

Karlik 1997

Glaucoma

2

ALT

180

Latanoprost before (24.1)

vs

apraclonidine before (23.2)

Karlik 1998

Glaucoma

2

ALT

180

Latanoprost before

vs

apraclonidine before

Kitazawa 1990

POAG

2

ALT

180

Apraclonidine before and after (24.2 ± 9.0)

vs

placebo before and after (23.2 ± 6.8)

Ma 1999

Glaucoma

4

ALT

180

Brimonidine before and after (24.9)

vs

brimonidine before, placebo after (24.8)

vs

placebo before, brimonidine after (24.1)

vs

placebo before and after (24.6)

Metcalfe 1989

Uncontrolled OAG

2

ALT

180

Acetazolamide before (23.6 ± 6.1)

vs

placebo before (23.7 ± 6.5)

Raspiller 1992

POAG

2

ALT

360

ALO 2145 (apraclonidine) before and after (20.1 ± 4.07)

vs

placebo before and after (25.0 ± 5.47)

Ren 1999

POAG

2

ALT

180

Apraclonidine before (23.2 ± 4.5)

vs

pilocarpine before (21.7 ± 3.5)

Robin 1987

OAG

2

ALT

360

ALO 2145 (apraclonidine) before and after (26.4 ± 3.0)

vs

placebo before and after (27.9 ± 6.9)

Robin 1991

OAG with disc and visual field damage

5

ALT

360

Apraclonidine before and after (27.2 ± 5.1)

vs

timolol before and after (27.6 ± 4.1)

vs

pilocarpine before and after (27.1 ± 5.1)

vs

dipivefrin before and after (25.9 ± 3.0)

vs

acetazolamide before and after (25.7 ± 3.9)

Yalvaç 1996

POAG

3

ALT

360 and 180

Apraclonidine before and after, 180° ALT (26.1 ± 5.1)

vs

placebo before and after, 180° ALT (25.6 ± 3.4)

vs

apraclonidine before and after, 360° ALT (26.4 ± 3.1)

ALT: argon laser trabeculoplasty; IOP: intraocular pressure; OAG: open‐angle glaucoma; POAG: primary open‐angle glaucoma; SLT: selective laser trabeculoplasty.

Figures and Tables -
Table 1. Study Comparison
Comparison 1. Medication versus placebo (regardless of timing)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Intraocular pressure (IOP) increase of ≥ 5 mmHg within 2 hours after laser trabeculoplasty (LTP) Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

1.1 Alpha‐2 agonists vs placebo

2

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 IOP increase of ≥ 10 mmHg within 2 hours after LTP Show forest plot

4

446

Risk Ratio (M‐H, Random, 95% CI)

0.05 [0.01, 0.20]

2.1 Acetazolamide vs placebo

1

100

Risk Ratio (M‐H, Random, 95% CI)

0.03 [0.00, 0.52]

2.2 Alpha‐2 agonists vs placebo

3

346

Risk Ratio (M‐H, Random, 95% CI)

0.06 [0.01, 0.27]

3 Mean change in IOP from pre‐LTP to measurements taken within 2 hours after LTP Show forest plot

4

Mean Difference (Random, 95% CI)

Subtotals only

3.1 Apraclonidine vs placebo (mmHg)

4

151

Mean Difference (Random, 95% CI)

‐7.43 [‐10.60, ‐4.27]

4 IOP increase of ≥ 5 mmHg two to 24 hours after LTP Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Alpha‐2 agonists vs placebo

5

634

Risk Ratio (M‐H, Random, 95% CI)

0.17 [0.09, 0.31]

5 IOP elevation of ≥ 10 mmHg two to 24 hours after LTP Show forest plot

9

817

Risk Ratio (M‐H, Random, 95% CI)

0.22 [0.11, 0.42]

5.1 Alpha‐2 agonists vs placebo

7

727

Risk Ratio (M‐H, Random, 95% CI)

0.19 [0.07, 0.50]

5.2 Dorzolamide vs placebo

1

40

Risk Ratio (M‐H, Random, 95% CI)

0.27 [0.01, 5.22]

5.3 Pilocarpine vs no treatment

1

50

Risk Ratio (M‐H, Random, 95% CI)

0.23 [0.07, 0.71]

6 Mean change in IOP from pre‐LTP to measurements two to 24 hours after LTP Show forest plot

4

Mean Difference (Random, 95% CI)

Subtotals only

6.1 Apraclonidine vs placebo (mmHg)

4

151

Mean Difference (Random, 95% CI)

‐5.32 [‐7.37, ‐3.28]

Figures and Tables -
Comparison 1. Medication versus placebo (regardless of timing)
Comparison 2. Medication versus medication: brimonidine versus apraclonidine (regardless of timing)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Intraocular pressure (IOP) increase of ≥ 5 mmHg within 2 hours after laser trabeculoplasty (LTP) Show forest plot

2

71

Risk Ratio (M‐H, Random, 95% CI)

2.28 [0.32, 16.03]

2 Mean change in IOP from pre‐LTP to measurements taken within 2 hours after LTP (mmHg) Show forest plot

2

71

Mean Difference (IV, Random, 95% CI)

‐0.69 [‐2.56, 1.17]

Figures and Tables -
Comparison 2. Medication versus medication: brimonidine versus apraclonidine (regardless of timing)
Comparison 3. Medication versus medication: apraclonidine versus pilocarpine (regardless of timing)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mean change in intraocular pressure (IOP) from pre‐laser trabeculoplasty (LTP) to measurements taken within 2 hours after LTP (mmHg) Show forest plot

2

277

Mean Difference (Random, 95% CI)

0.61 [‐0.44, 1.66]

2 IOP increase of ≥ 5 mmHg two to 24 hours after LTP Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3 IOP increase of ≥ 10 mmHg two to 24 hours after LTP Show forest plot

2

390

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.14, 5.63]

4 Mean change in IOP from pre‐LTP to measurements taken two to 24 hours after LTP (mmHg) Show forest plot

2

Mean Difference (Fixed, 95% CI)

Subtotals only

Figures and Tables -
Comparison 3. Medication versus medication: apraclonidine versus pilocarpine (regardless of timing)
Comparison 4. Timing comparison: medication before versus medication after

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Intraocular pressure (IOP) increase of ≥ 5 mmHg two to 24 hours after laser trabeculoplasty (LTP) Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Alpha‐2 agonists

4

319

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.25, 2.63]

2 IOP increase of ≥ 10 mmHg two to 24 hours after LTP Show forest plot

4

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Alpha‐2 agonists

4

319

Risk Ratio (M‐H, Random, 95% CI)

1.55 [0.19, 12.43]

3 Mean change in IOP from pre‐LTP to measurements taken more than 2 hours but within 24 hours after LTP (mmHg) Show forest plot

3

Mean Difference (Random, 95% CI)

Subtotals only

3.1 Alpha‐2 agonists (mmHg)

3

198

Mean Difference (Random, 95% CI)

‐1.07 [‐2.51, 0.37]

Figures and Tables -
Comparison 4. Timing comparison: medication before versus medication after
Comparison 5. Adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Conjunctival blanching (brimonidine vs placebo) Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

Figures and Tables -
Comparison 5. Adverse events