Medical interventions for primary open angle glaucoma and ocular hypertension

Clemens Vass; Cornelia Hirn; Thomas Sycha; Oliver Findl; Stefan Sacu; Peter Bauer; Leopold Schmetterer

doi:10.1002/14651858.CD003167.pub3

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Analysis 1.1

Comparison 1 Beta‐blockers versus placebo or untreated, Outcome 1 Incidence of visual field defect progression.

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Analysis 1.2

Comparison 1 Beta‐blockers versus placebo or untreated, Outcome 2 Drop‐out due to drug‐related adverse events.

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Analysis 1.3

Comparison 1 Beta‐blockers versus placebo or untreated, Outcome 3 Sensitivity analysis concerning the incidence of visual field defect progression.

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Analysis 1.4

Comparison 1 Beta‐blockers versus placebo or untreated, Outcome 4 Long‐term studies concerning the incidence of visual field progression.

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Analysis 2.1

Comparison 2 Comparison of timolol and carteolol, Outcome 1 Incidence of visual field defect progression.

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Analysis 3.1

Comparison 3 Comparison of timolol and levobunolol, Outcome 1 Incidence of visual field defect progression.

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Analysis 3.2

Comparison 3 Comparison of timolol and levobunolol, Outcome 2 Drop‐out due to drug‐related adverse events.

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Analysis 4.1

Comparison 4 Comparisons of timolol and betaxolol, Outcome 1 Change of visual field mean sensitivity.

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Analysis 4.2

Comparison 4 Comparisons of timolol and betaxolol, Outcome 2 Drop‐out due to drug‐related adverse events.

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Analysis 5.1

Comparison 5 Comparison of timolol and brimonidine, Outcome 1 Incidence of visual field defect progression.

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Analysis 5.2

Comparison 5 Comparison of timolol and brimonidine, Outcome 2 Drop‐out due to drug‐related adverse events.

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Analysis 6.1

Comparison 6 All treatments versus placebo or untreated, Outcome 1 Incidence of visual field defect progression.

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Analysis 6.2

Comparison 6 All treatments versus placebo or untreated, Outcome 2 Sensitivity analysis concerning the incidence of visual field progression.

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Analysis 6.3

Comparison 6 All treatments versus placebo or untreated, Outcome 3 Sensitivity analysis concerning the incidence of visual field progression; without OHTS study.

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Table 1. Methodological quality of included studies

Criteria	Number of trials
Allocation concealment adequate	16 / 26
Baseline comparability stated	19 / 26
Analysis: intention‐to‐treat	9 / 26
Withdrawals adequately reported	17 / 26
Drop‐out rate below 10%	1 / 26
Low methodological quality	16 / 26

Table 1. Methodological quality of included studies

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Table 2. Summary table for analyses of outcomes

Comparison	POAG	OHT	POAG & OHT	Drop‐out due to AE
Beta‐blockers vs. placebo or untreated		0.67 (0.45 to 1.00; n=935)		1.24 (0.59 to 2.58; n=503)
Longterm trials		0.67 (0.45 to 1.01; n=882)
Sensitivity analysis		0.64 (0.34 to 1.19; n=499)
Timolol vs. placebo or untreated		0.66 (0.41 to 1.05; n=579)		2.48 (0.61 to 10.10; n=147)
Timolo vs. carteolol	0.18 (0.05 to 0.62; n=171) +
Timolol vs. levobunolol			2.20 (1.17 to 4.14; n=290) #	0.80 (0.34 to 1.87; n=290)
Timolol vs. betaxolol	0.07dB (‐0.43dB to 0.57dB; n=158) $			2.40 (1.04 to 5.53; n=238) §
Timolol vs. brimonidine			1.11 (0.60 to 2.04; n=671)	0.21 (0.14 to 0.31; n=957) ++
All treatment vs. placebo or untreated		0.62 (0.47 to 0.81; n=3648)
Sensitivity analysis		0.58 (0.42 to 0.81; n=3212)
Sensitivity analysis without OHTS		0.66 (0.44 to 0.98; n=1576)
+ favours timolol; # favours levobunolol;	$ 14 participants with OHT included	§ favours betaxolol	++ favours timolol

Table 2. Summary table for analyses of outcomes

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Comparison 1. Beta‐blockers versus placebo or untreated

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of visual field defect progression Show forest plot	8	935	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.67 [0.45, 1.00]

1.1 Timolol versus placebo or untreated	7	579	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.66 [0.41, 1.05]
1.2 Betaxolol versus placebo or untreated	1	356	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.70 [0.32, 1.51]
2 Drop‐out due to drug‐related adverse events Show forest plot	4	503	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.24 [0.59, 2.58]

2.1 Timolol versus placebo	3	147	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.48 [0.61, 10.10]
2.2 Betaxolol versus placebo	1	356	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.95 [0.40, 2.26]
3 Sensitivity analysis concerning the incidence of visual field defect progression Show forest plot	4	499	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.64 [0.34, 1.19]

3.1 Timolol versus placebo or untreated	3	143	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.54 [0.19, 1.54]
3.2 Betaxolol versus placebo or untreated	1	356	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.70 [0.32, 1.51]
4 Long‐term studies concerning the incidence of visual field progression Show forest plot	6	882	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.67 [0.45, 1.01]

Comparison 1. Beta‐blockers versus placebo or untreated

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Comparison 2. Comparison of timolol and carteolol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of visual field defect progression Show forest plot	2	171	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.18 [0.05, 0.62]

Comparison 2. Comparison of timolol and carteolol

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Comparison 3. Comparison of timolol and levobunolol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of visual field defect progression Show forest plot	2	290	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.20 [1.17, 4.14]

2 Drop‐out due to drug‐related adverse events Show forest plot	2	290	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.80 [0.34, 1.87]

Comparison 3. Comparison of timolol and levobunolol

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Comparison 4. Comparisons of timolol and betaxolol

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change of visual field mean sensitivity Show forest plot	6	258	Mean Difference (IV, Fixed, 95% CI)	0.07 [‐0.43, 0.57]

2 Drop‐out due to drug‐related adverse events Show forest plot	5	238	Peto Odds Ratio (Peto, Fixed, 95% CI)	2.40 [1.04, 5.53]

Comparison 4. Comparisons of timolol and betaxolol

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Comparison 5. Comparison of timolol and brimonidine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of visual field defect progression Show forest plot	2	671	Peto Odds Ratio (Peto, Fixed, 95% CI)	1.11 [0.60, 2.04]

2 Drop‐out due to drug‐related adverse events Show forest plot	3	957	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.21 [0.14, 0.31]

Comparison 5. Comparison of timolol and brimonidine

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Comparison 6. All treatments versus placebo or untreated

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Incidence of visual field defect progression Show forest plot	10	3648	Peto Odds Ratio (Peto, Fixed, 95% CI)	0.62 [0.47, 0.81]

2 Sensitivity analysis concerning the incidence of visual field progression Show forest plot	6	3212	Odds Ratio (M‐H, Fixed, 95% CI)	0.58 [0.42, 0.81]

3 Sensitivity analysis concerning the incidence of visual field progression; without OHTS study Show forest plot	5	1576	Odds Ratio (M‐H, Fixed, 95% CI)	0.66 [0.44, 0.98]

Comparison 6. All treatments versus placebo or untreated

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