Interventions for central serous chorioretinopathy: a network meta‐analysis

Mahsa Salehi; Adam S Wenick; Hua Andrew Law; Jennifer R Evans; Peter Gehlbach

doi:10.1002/14651858.CD011841.pub2

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Figure 1

Theoretical treatment network.

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Figure 2

Study flow diagram.

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Figure 3

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

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Figure 4

Visual acuity network: network plot, interval plot, contribution matrix and risk of bias.

AVG: Anti‐VEGF PDT: photodynamic therapy LAS: laser AVPDT: anti‐VEGF plus PDT.

1 = control; 2 = anti‐VEGF; 3 = PDT; 4 = laser; 5 = anti‐VEGF plus PDT.

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Figure 5

Recurrence CSC network: network plot, interval plot, contribution matrix and risk of bias.

AVG: Anti‐VEGF; PDT: photodynamic therapy; LAS: laser: CTL: control.

1 = control; 2 = anti‐VEGF; 3 = PDT; 4 = laser.

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Analysis 1.1

Comparison 1 Anti‐VEGF versus observation, Outcome 1 Mean change in BCVA at 12 months.

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Analysis 1.2

Comparison 1 Anti‐VEGF versus observation, Outcome 2 Mean change in CRT at 12 months.

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Analysis 2.1

Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 1 Mean change in BCVA at 12 months.

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Analysis 2.2

Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 2 Recurrence of CSC at 12 months.

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Analysis 2.3

Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 3 Persistent CSC at 12 months.

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Analysis 2.4

Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 4 Mean change in CRT at 12 months.

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Analysis 3.1

Comparison 3 Anti‐VEGF plus 50% PDT versus 50% PDT, Outcome 1 Mean change in BCVA at 12 months.

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Analysis 3.2

Comparison 3 Anti‐VEGF plus 50% PDT versus 50% PDT, Outcome 2 Persistent CSC at 12 months.

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Analysis 3.3

Comparison 3 Anti‐VEGF plus 50% PDT versus 50% PDT, Outcome 3 Mean change in CRT at 12 months.

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Analysis 4.1

Comparison 4 Six‐dose anti‐VEGF versus four‐dose anti‐VEGF, Outcome 1 Mean change in BCVA at 12 months.

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Analysis 4.2

Comparison 4 Six‐dose anti‐VEGF versus four‐dose anti‐VEGF, Outcome 2 Mean change in CRT at 12 months.

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Analysis 5.1

Comparison 5 50% PDT versus sham treatment, Outcome 1 Mean BCVA at 12 months.

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Analysis 5.2

Comparison 5 50% PDT versus sham treatment, Outcome 2 Recurrence/persistence CSC at 12 months.

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Analysis 5.3

Comparison 5 50% PDT versus sham treatment, Outcome 3 Mean CRT at 12 months.

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Analysis 6.1

Comparison 6 30% PDT versus PDT, Outcome 1 Mean BCVA at 12 months.

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Analysis 6.2

Comparison 6 30% PDT versus PDT, Outcome 2 Recurrence of CSC at 12 months.

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Analysis 6.3

Comparison 6 30% PDT versus PDT, Outcome 3 Mean change in CRT at 12 months.

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Analysis 7.1

Comparison 7 50% PDT versus PDT, Outcome 1 Mean BCVA at 12 months.

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Analysis 7.2

Comparison 7 50% PDT versus PDT, Outcome 2 Recurrence of CSC at 12 months.

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Analysis 7.3

Comparison 7 50% PDT versus PDT, Outcome 3 Mean change in CRT at 12 months.

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Analysis 8.1

Comparison 8 30% PDT versus 50% PDT, Outcome 1 Mean change in BCVA at 12 months.

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Analysis 8.2

Comparison 8 30% PDT versus 50% PDT, Outcome 2 Recurrence of CSC at 12 months.

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Analysis 8.3

Comparison 8 30% PDT versus 50% PDT, Outcome 3 Persistent CSC at 12 months.

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Analysis 8.4

Comparison 8 30% PDT versus 50% PDT, Outcome 4 Mean change in CRT at 12 months.

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Analysis 9.1

Comparison 9 Laser versus observation or sham treatment, Outcome 1 Mean change in BCVA at 12 months.

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Analysis 9.2

Comparison 9 Laser versus observation or sham treatment, Outcome 2 Recurrence of CSC at 12 months.

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Analysis 9.3

Comparison 9 Laser versus observation or sham treatment, Outcome 3 Mean change in CRT at 12 months.

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Analysis 10.1

Comparison 10 Indirect argon laser versus direct argon laser, Outcome 1 Recurrence of CSC at 12 months.

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Analysis 11.1

Comparison 11 Comparison of different laser wavelengths, Outcome 1 Recurrence of CSC at 12 months.

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Analysis 12.1

Comparison 12 Antioxidant supplements versus placebo, Outcome 1 BCVA at 12 months.

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Analysis 12.2

Comparison 12 Antioxidant supplements versus placebo, Outcome 2 Recurrence at 12 months.

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Analysis 12.3

Comparison 12 Antioxidant supplements versus placebo, Outcome 3 Persistence at 12 months.

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Analysis 12.4

Comparison 12 Antioxidant supplements versus placebo, Outcome 4 CRT at 12 months.

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Analysis 13.1

Comparison 13 Beta‐blocker versus placebo, Outcome 1 Mean BCVA at 12 months.

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Analysis 13.2

Comparison 13 Beta‐blocker versus placebo, Outcome 2 Recurrence of CSC at 12 months.

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Analysis 13.3

Comparison 13 Beta‐blocker versus placebo, Outcome 3 BCVA ≥ 20/40 at 12 months.

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Analysis 14.1

Comparison 14 Carbonic anhydrase inhibitors versus placebo, Outcome 1 Recurrent/persistent CSC at 12 months.

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Analysis 15.1

Comparison 15 Helicobacter pylori treatment versus placebo or observation, Outcome 1 Mean BCVA at 12 months.

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Analysis 15.2

Comparison 15 Helicobacter pylori treatment versus placebo or observation, Outcome 2 Persistent CSC at 12 months.

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Summary of findings for the main comparison. Interventions for central serous chorioretinopathy: direct comparisons

Interventions for central serous chorioretinopathy: direct comparisons
Patient or population: people with central serous chorioretinopathy Settings: eye hospital
Comparison (intervention vs. comparator)	Anticipated absolute effects (95% CI)		Effect estimate from direct comparison			Comments
	Anticipated absolute effects (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality
	Risk with comparator	Mean difference (95% CI) Negative values are in favor of intervention; positive values in favor of comparator	Relative effect (95% CI)	No of participants (studies)	Quality
Change in visual acuity at 12 months (logMAR)
Anti‐VEGF vs. observation	‐	0.01 LogMAR (‐0.02 to 0.03)	‐	64 (2)	Low^1,2	Both studies enrolled participants with acute CSC and reported mean change in visual acuity at 6 months
Anti‐VEGF vs. low‐fluence PDT	‐	0.03 logMAR (‐0.08 to 0.15)	‐	56 (2)	Low^1,2	Both studies enrolled participants with chronic CSC
Anti‐VEGF and 50% PDT vs. 50% PDT	‐	0.30 logMAR (0.09 to 0.51)	‐	15 (1)	Low^1,2	Participants had chronic CSC
6‐dose anti‐VEGF vs. 4‐dose anti‐VEGF	‐	‐0.02 logMAR (‐0.31 to 0.27)	‐	12 (1)	Low^1,2	Participants had chronic CSC and were followed to 6 months
50% PDT vs. observation or sham treatment	‐	‐0.10 logMAR (‐0.18 to ‐0.02)	‐	58 (1)	Low^1,2	Participants had acute CSC
30% PDT vs. PDT	‐	‐0.16 logMAR (‐0.22 to ‐0.10)	‐	60 (1)	Low^1,2	Type of CSC not specified
30% PDT vs. 50% PDT	‐	‐0.12 logMAR (‐0.15 to ‐0.08)	‐	60 (1)	Low^1,2	Type of CSC not specified
50% PDT vs. PDT	‐	0.04 logMAR (‐0.04 to 0.12	‐	60 (1)	Low^1,2	Type of CSC not specified
Selective retina therapy vs. observation	‐	‐0.13 logMAR (‐0.24 to ‐0.01)	‐	30 (1)	Low^1,2	Participants had acute CSC, followed up to 3 months
Micropulse diode laser vs. sham laser	‐	‐0.38 logMAR (‐0.56 to ‐0.20)	‐	15 (1)	Low^1,2	Participants had chronic CSC
Antioxidant vs. placebo	‐	0.01 logMAR (‐0.04 to 0.06)	‐	14 (1)	Low^1,2	Lutein and acute CSC
Propranolol vs. placebo	‐	0.01 logMAR (‐0.07 to 0.09)	‐	60 (1)	Low^1,2	Type of CSC not specified
Carbonic anhydrase inhibitors vs. placebo	See comment	‐	‐	13 (1)	‐	Outcome not reported
Helicobacter pylori treatment vs. placebo	‐	‐0.04 logMAR (‐0.07 to ‐0.02)	‐	103 (2)	Low^1,2	Participants had acute CSC, follow‐up 12‐16 weeks
Comparison (intervention vs. comparator)	Anticipated absolute effects (95% CI)		Effect estimate from direct comparison			Comments
Comparison (intervention vs. comparator)	Risk with comparator*	Risk with intervention	Relative effect (95% CI)	No of participants (studies)	Quality	Comments
Persistent CSC at 12 months
Anti‐VEGF vs. observation	See comment	‐	‐	64 (2)	‐	Participants had acute CSC. Both trials reported that all participants in treatment and control groups were resolved by 6 months
Anti‐VEGF vs. low‐fluence PDT	111 per 1000	688 per 1000 (179 to 1000)	RR 6.19 (1.61 to 23.81)	34 (1)	Low^1,2	Participants had chronic CSC
Anti‐VEGF and 50% PDT vs. 50% PDT	143 per 1000	126 (10 to 1000)	RR 0.88 (0.07 to 11.54)	15 (1)	Very low^1,2,3	Participants had chronic CSC
6‐dose anti‐VEGF vs. 4‐dose anti‐VEGF	See comment	‐	‐	12 (1)	‐	Outcome not reported
50% PDT vs. sham treatment	211 per 1000	25 per 1000 (2 to 215)	RR 0.12 (0.01 to 1.02)	58 (1)	Low^1,2	Participants had acute CSC
30% PDT vs. PDT	See comment	‐	‐	60 (1)	‐	Outcome not reported
30% PDT vs. 50% PDT	See comment	‐	‐	60 (1)	‐	Outcome not reported
50% PDT vs. PDT	See comment	‐	‐	60 (1)	‐	Outcome not reported
Selective retina therapy vs. observation	See comment	‐	‐	30 (1)	‐	Outcome not reported
Micropulse diode laser	See comment	‐	‐	15 (1)	‐	Outcome not reported
Antioxidant vs. placebo	See comment	‐	‐	51 (1)	‐	People in the antioxidant group were less likely to have "complete resolution" at 3 months (RR 0.35, 95% CI 0.13 to 0.95; 51 participants)
Propranolol vs. placebo	See comment	‐	‐	60 (1)	‐	Outcome not reported
Brinzolamide vs. placebo	167 per 1000	48 (2 to 1000)	RR 0.29 (0.01 to 6.07)	13 (1)	Very low^2,3	Participants had acute CSC
Helicobacter pylori treatment vs. placebo	314 per 1000	210 (113 to 383)	RR 0.67 (0.36 to 1.22)	103 (2)	Low^1,2	Participants had acute CSC
Comparison (intervention vs. comparator)	Anticipated absolute effects (95% CI)		Effect estimate from direct comparison
Comparison (intervention vs. comparator)	Risk with comparator*	Risk with intervention	Relative effect (95% CI)	No of participants (studies)	Quality	Comment
Recurrent CSC at 12 months
Anti‐VEGF vs. observation	See comment	‐	‐	64 (2)	‐	Outcome not reported
Anti‐VEGF vs. low‐fluence PDT	See comment	‐	‐	56 (2)	Very low^1,2,4	Participants had chronic CSC. The 2 studies had different results for this outcome (I² = 71%). In Bae 2011, there was a much higher risk of recurrence in the anti‐VEGF group (ranibizumab) compared with the PDT group (RR 19.83, 95% CI 1.19 to 330.50; 21 eyes); in Semeraro 2012, there was also an increased risk of recurrence in the anti‐VEGF (bevacizumab) group but the size of the effect was much smaller and the CIs include 1 (no effect) (RR 1.46, 95% CI 0.59 to 3.58; 22 eyes)
Anti‐VEGF and 50% PDT vs. 50% PDT	See comment	‐	‐	15 (1)	‐	Outcome not reported
6‐dose anti‐VEGF vs. 4‐dose anti‐VEGF	See comment	‐	‐	12 (1)	‐	Outcome not reported
50% PDT vs. sham treatment	267 per 1000	27 per 1000 (3 to 216)	RR 0.10 (0.01 to 0.81)	53 (1)	Low^1,2	Participants had acute CSC
30% PDT vs. PDT	See comment	‐	‐	60 (1)	‐	Outcome not reported
30% PDT vs. 50% PDT	See comment	‐	‐	60 (1)	‐	Outcome not reported
50% PDT vs. PDT	270 per 1000	338 per 1000 (154 to 737)	RR 1.25 (0.57 to 2.73)	60 (1)	‐	Type of CSC not specified
Selective retina therapy vs. observation	See comment	‐	‐	30 (1)	‐	Outcome not reported
Micropulse diode laser	See comment	‐	‐	15 (1)	‐	Outcome not reported
Antioxidant vs. placebo	143 per 1000	46 (4 to 456)	RR 0.32 (0.03 to 3.19)	36 (1)	Very low^2,3	Participants had acute CSC
Propranolol vs. placebo	167 per 1000	100 (27 to 382)	RR 0.60 (0.16 to 2.29)	60 (1)	Low^1,2	Type of CSC not reported
Brinzolamide vs. placebo	314 per 1000	140 (20 to 953)	RR 0.21 (0.03 to 1.43	13 (1)	Low^1,2	Participants had acute CSC
Helicobacter pylori treatment vs. placebo	See comment	‐	‐	103 (2)	‐	Outcome not reported
Adverse effects
All studies reported no ocular or systematic adverse effects, or did not comment on adverse effects
anti‐VEGF: anti‐vascular endothelial growth factor; CI: confidence interval; CSC: central serous chorioretinopathy; logMAR: logarithm of the minimal angle of resolution; PDT: photodynamic therapy; RR: risk ratio. * Risk was estimated from the comparator group in the included studies 1 Downgraded for imprecision (‐1) 2 Downgraded for risk of bias (‐1) 3 Downgraded for imprecision (‐2) 4 Downgraded for inconsistency (‐1)

Summary of findings for the main comparison. Interventions for central serous chorioretinopathy: direct comparisons

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Table 1. Assessment of transitivity across treatment comparisons: visual acuity

Treatment comparison	Study	Type of CSC	Date study conducted	Industry sponsored
Anti‐VEGF vs. PDT	Bae 2011 Semeraro 2012	Chronic Chronic	2009‐2012 2009‐2010	Yes NR
PDT vs. no treatment	Chan 2008	Acute	2004‐2005	NR
Laser vs. no treatment	Robertson 1983	Acute	1977‐1981	No
One additional study for the comparison PDT vs. no treatment was reported in abstract form only and no data on outcome so was not included in the network meta‐analysis (Boscia 2008). anti‐VEGF: anti‐vascular endothelial growth factor; CSC: central serous chorioretinopathy; NR: not reported; PDT: photodynamic therapy.

Table 1. Assessment of transitivity across treatment comparisons: visual acuity

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Table 2. Comparative effects of ocular interventions for central serous chorioretinopathy: visual acuity

Anti‐VEGF	‐0.08 (‐0.14 to ‐0.01)	‐0.20 (‐0.30 to ‐0.11)	0.00 (‐0.02 to 0.03)	0.22 (0.01 to 0.44)
0.08 (0.01 to 0.14)	PDT	‐0.13 (‐0.24 to ‐0.01)	0.08 (0.01 to 0.15)	0.30 (0.09 to 0.51)
0.20 (0.11 to 0.30)	0.13 (0.01 to 0.24)	Laser	0.21 (0.11 to 0.31)	0.43 (0.19 to 0.66)
‐0.00 (‐0.03 to 0.02)	‐0.08 (‐0.15 to ‐0.01)	‐0.21 (‐0.31 to ‐0.11)	Anti‐VEGF and PDT	0.22 (0.00 to 0.44)
‐0.22 (‐0.44 to ‐0.01)	‐0.30 (‐0.51 to ‐0.09)	‐0.43 (‐0.66 to ‐0.19)	‐0.22 (‐0.44 to ‐0.00)	Control (no treatment or sham treatment)
Effect estimate is the mean difference (95% confidence interval). Negative values favor the first intervention. In the lower left hand triangle, the first intervention is anti‐VEGF, PDT, laser etc. In the upper right hand triangle, the first intervention is control, anti‐VEGF and PDT, laser etc. So, for example, visual acuity with anti‐VEGF was 0.22 logMAR units better than control 95% CI 0.44 better to 0.01 better. anti‐VEGF: anti‐vascular endothelial growth factor; logMAR: logarithm of the minimal angle of resolution; PDT: photodynamic therapy.

Table 2. Comparative effects of ocular interventions for central serous chorioretinopathy: visual acuity

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Table 3. Assessment of transitivity across treatment comparisons: recurrence

Treatment comparison	Study	Type of CSC	Date study conducted	Industry sponsored
Anti‐VEGF vs. no treatment	Kim 2013 Lim 2010	Acute Acute	2010‐2011 2008	No No
Anti‐VEGF vs. PDT	Bae 2011 Semeraro 2012	Chronic Chronic	2009‐2012 2009‐2010	Yes NR
Anti‐VEGF + PDT vs. PDT alone	Coskun 2014	Chronic	NR (published 2014)	NR
PDT vs. no treatment	Chan 2008	Acute	2004‐2005	NR
Laser vs. no treatment	Klatt 2011 Robertson 1983 Roisman 2013	Acute Acute Chronic	2007‐2008 1977‐1981 NR (published 2013)	NR No NR
One additional study for the comparison PDT vs no treatment was reported in abstract form only and no data on outcome so was not included in the network meta‐analysis (Boscia 2008). anti‐VEGF: anti‐vascular endothelial growth factor; CSC: central serous chorioretinopathy; NR: not reported; PDT: photodynamic therapy.

Table 3. Assessment of transitivity across treatment comparisons: recurrence

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Table 4. Comparative effects of ocular interventions for CSC: recurrence

Anti‐VEGF	0.27 (0.02 to 3.73)	3.34 (0.01 to 788.57)	2.67 (0.03 to 234.08)
3.77 (0.27 to 52.94)	PDT	12.58 (0.11 to 1503.87)	10.07 (0.27 to 371.91)
0.30 (0.00 to 70.79)	0.08 (0.00 to 9.50)	Laser	0.80 (0.03 to 18.46)
0.37 (0.00 to 32.83)	0.10 (0.00 to 3.67)	1.25 (0.05 to 28.85)	Control
Effect estimate is the risk ratio (95% CI). anti‐VEGF: anti‐vascular endothelial growth factor; logMAR: logarithm of the minimal angle of resolution; PDT: photodynamic therapy.

Table 4. Comparative effects of ocular interventions for CSC: recurrence

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Comparison 1. Anti‐VEGF versus observation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean change in BCVA at 12 months Show forest plot	2	64	Mean Difference (IV, Fixed, 95% CI)	0.01 [‐0.02, 0.03]

2 Mean change in CRT at 12 months Show forest plot	2	64	Mean Difference (IV, Fixed, 95% CI)	8.73 [‐18.08, 35.54]

Comparison 1. Anti‐VEGF versus observation

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Comparison 2. Anti‐VEGF versus low fluence PDT

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean change in BCVA at 12 months Show forest plot	2	56	Mean Difference (IV, Fixed, 95% CI)	0.03 [‐0.08, 0.15]

2 Recurrence of CSC at 12 months Show forest plot	2		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Persistent CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Mean change in CRT at 12 months Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 2. Anti‐VEGF versus low fluence PDT

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Comparison 3. Anti‐VEGF plus 50% PDT versus 50% PDT

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean change in BCVA at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Persistent CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Mean change in CRT at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 3. Anti‐VEGF plus 50% PDT versus 50% PDT

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Comparison 4. Six‐dose anti‐VEGF versus four‐dose anti‐VEGF

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean change in BCVA at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Mean change in CRT at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 4. Six‐dose anti‐VEGF versus four‐dose anti‐VEGF

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Comparison 5. 50% PDT versus sham treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean BCVA at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Recurrence/persistence CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2.1 Recurrence of CSC at 12 months	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 Persistent CSC at 12 months	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Mean CRT at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 5. 50% PDT versus sham treatment

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Comparison 6. 30% PDT versus PDT

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean BCVA at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Recurrence of CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Mean change in CRT at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 6. 30% PDT versus PDT

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Comparison 7. 50% PDT versus PDT

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean BCVA at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Recurrence of CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Mean change in CRT at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 7. 50% PDT versus PDT

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Comparison 8. 30% PDT versus 50% PDT

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean change in BCVA at 12 months Show forest plot	2	177	Mean Difference (IV, Fixed, 95% CI)	‐0.12 [‐0.15, ‐0.08]

2 Recurrence of CSC at 12 months Show forest plot	2	153	Risk Ratio (M‐H, Fixed, 95% CI)	2.50 [1.54, 4.06]

3 Persistent CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 Mean change in CRT at 12 months Show forest plot	2	177	Mean Difference (IV, Fixed, 95% CI)	44.90 [42.57, 47.23]

Comparison 8. 30% PDT versus 50% PDT

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Comparison 9. Laser versus observation or sham treatment

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean change in BCVA at 12 months Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Recurrence of CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Mean change in CRT at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 9. Laser versus observation or sham treatment

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Comparison 10. Indirect argon laser versus direct argon laser

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Recurrence of CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 10. Indirect argon laser versus direct argon laser

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Comparison 11. Comparison of different laser wavelengths

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Recurrence of CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Yellow compared with red	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Yellow compared with green	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 Red compared with green	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 11. Comparison of different laser wavelengths

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Comparison 12. Antioxidant supplements versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 BCVA at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Recurrence at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 Persistence at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

4 CRT at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 12. Antioxidant supplements versus placebo

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Comparison 13. Beta‐blocker versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean BCVA at 12 months Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Recurrence of CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 BCVA ≥ 20/40 at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 13. Beta‐blocker versus placebo

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Comparison 14. Carbonic anhydrase inhibitors versus placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Recurrent/persistent CSC at 12 months Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 Recurrence of CSC at 12 months	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 Persistent CSC at 12 months	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 14. Carbonic anhydrase inhibitors versus placebo

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Comparison 15. Helicobacter pylori treatment versus placebo or observation

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Mean BCVA at 12 months Show forest plot	2	103	Mean Difference (IV, Fixed, 95% CI)	‐0.04 [‐0.07, ‐0.02]

2 Persistent CSC at 12 months Show forest plot	2	103	Risk Ratio (M‐H, Fixed, 95% CI)	0.67 [0.36, 1.22]

Comparison 15. Helicobacter pylori treatment versus placebo or observation

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