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. 2015 Dec 22;2015(12):CD011841.
doi: 10.1002/14651858.CD011841.pub2.

Interventions for central serous chorioretinopathy: a network meta-analysis

Mahsa Salehi  1 , Adam S Wenick, Hua Andrew Law, Jennifer R Evans, Peter Gehlbach
Affiliations

Interventions for central serous chorioretinopathy: a network meta-analysis

Mahsa Salehi et al. Cochrane Database Syst Rev. .

Update in

Abstract

Background: Central serous chorioretinopathy (CSC) is characterized by serous detachment of the neural retina with dysfunction of the choroid and retinal pigment epithelium (RPE). The effects on the retina are usually self limited, although some people are left with irreversible vision loss due to progressive and permanent photoreceptor damage or RPE atrophy. There have been a variety of interventions used in CSC, including, but not limited to, laser treatment, photodynamic therapy (PDT), and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents. However, it is not known whether these or other treatments offer significant advantages over observation or other interventions. At present there is no evidence-based consensus on the management of CSC. Due in large part to the propensity for CSC to resolve spontaneously or to follow a waxing and waning course, the most common initial approach to treatment is observation. It remains unclear whether this is the best approach with regard to safety and efficacy.

Objectives: To compare the relative effectiveness of interventions for central serous chorioretinopathy.

Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2015, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to October 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2015.

Selection criteria: Randomized controlled trials (RCTs) that compared any intervention for CSC with any other intervention for CSC or control.

Data collection and analysis: Two review authors independently selected studies and extracted data. We pooled data from all studies using a fixed-effect model. For interventions applied to the eye (i.e. not systemic interventions), we synthesized direct and indirect evidence in a network meta-analysis model.

Main results: We included 25 studies with 1098 participants (1098 eyes) and follow-up from 16 weeks to 12 years. Studies were conducted in Europe, North and South America, Middle East, and Asia. The trials were small (most trials enrolled fewer than 50 participants) and poorly reported; often it was unclear whether key aspects of the trial, such as allocation concealment, had been done. A substantial proportion of the trials were not masked.The studies considered a variety of treatments: anti-VEGF (ranibizumab, bevacizumab), PDT (full-dose, half-dose, 30%, low-fluence), laser treatment (argon, krypton and micropulse laser), beta-blockers, carbonic anhydrase inhibitors, Helicobactor pylori treatment, and nutritional supplements (Icaps, lutein); there were only one or two trials contributing data for each comparison. We downgraded for risk of bias and imprecision for most analyses, reflecting study limitations and imprecise estimates. Network meta-analysis (as planned in our protocol) did not help to resolve this uncertainty due to a lack of trials, and problems with intransitivity, particularly with respect to acute or chronic CSC.Low quality evidence from two trials suggested little difference in the effect of anti-VEGF (ranibizumab or bevacizumab) or observation on change in visual acuity at six months in acute CSC (mean difference (MD) 0.01 LogMAR (logarithm of the minimal angle of resolution), 95% confidence interval (CI) -0.02 to 0.03; 64 participants). CSC had resolved in all participants by six months. There were no significant adverse effects noted.Low quality evidence from one study (58 participants) suggested that half-dose PDT treatment of acute CSC probably results in a small improvement in vision (MD -0.10 logMAR, 95% CI -0.18 to -0.02), less recurrence (risk ratio (RR) 0.10, 95% CI 0.01 to 0.81) and less persistent CSC (RR 0.12, 95% CI 0.01 to 1.02) at 12 months compared to sham treatment. There were no significant adverse events noted.Low quality evidence from two trials (56 participants) comparing anti-VEGF to low-fluence PDT in chronic CSC found little evidence for any difference in visual acuity at 12 months (MD 0.03 logMAR, 95% CI -0.08 to 0.15). There was some evidence that more people in the anti-VEGF group had recurrent CSC compared to people treated with PDT but, due to inconsistency between trials, it was difficult to estimate an effect. More people in the anti-VEGF group had persistent CSC at 12 months (RR 6.19, 95% CI 1.61 to 23.81; 34 participants).Two small trials of micropulse laser, one in people with acute CSC and one in people with chronic CSC, provided low quality evidence that laser treatment may lead to better visual acuity (MD -0.20 logMAR, 95% CI -0.30 to -0.11; 45 participants). There were no significant adverse effects noted.Other comparisons were largely inconclusive.We identified 12 ongoing trials covering the following interventions: aflibercept and eplerenone in acute CSC; spironolactone, eplerenone, lutein, PDT, and micropulse laser in chronic CSC; and micropulse laser and oral mifepristone in two trials where type of CSC not clearly specified.

Authors' conclusions: CSC remains an enigmatic condition in large part due to a natural history of spontaneous improvement in a high proportion of people and also because no single treatment has provided overwhelming evidence of efficacy in published RCTs. While a number of interventions have been proposed as potentially efficacious, the quality of study design, execution of the study and the relatively small number of participants enrolled and followed to revealing endpoints limits the utility of existing data. It is not clear whether there is a clinically important benefit to treating acute CSC which often resolves spontaneously as part of its natural history. RCTs comparing individual treatments to the natural history would be valuable in identifying potential treatment groups for head-to-head comparison. Of the interventions studied to date, PDT or micropulse laser treatment appear the most promising for study in future trials.

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Conflict of interest statement

DECLARATIONS OF INTEREST None known.

Figures

1
1
Theoretical treatment network.
2
2
Study flow diagram.
3
3
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
4
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.
5
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.
1.1
1.1. Analysis
Comparison 1 Anti‐VEGF versus observation, Outcome 1 Mean change in BCVA at 12 months.
1.2
1.2. Analysis
Comparison 1 Anti‐VEGF versus observation, Outcome 2 Mean change in CRT at 12 months.
2.1
2.1. Analysis
Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 1 Mean change in BCVA at 12 months.
2.2
2.2. Analysis
Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 2 Recurrence of CSC at 12 months.
2.3
2.3. Analysis
Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 3 Persistent CSC at 12 months.
2.4
2.4. Analysis
Comparison 2 Anti‐VEGF versus low fluence PDT, Outcome 4 Mean change in CRT at 12 months.
3.1
3.1. Analysis
Comparison 3 Anti‐VEGF plus 50% PDT versus 50% PDT, Outcome 1 Mean change in BCVA at 12 months.
3.2
3.2. Analysis
Comparison 3 Anti‐VEGF plus 50% PDT versus 50% PDT, Outcome 2 Persistent CSC at 12 months.
3.3
3.3. Analysis
Comparison 3 Anti‐VEGF plus 50% PDT versus 50% PDT, Outcome 3 Mean change in CRT at 12 months.
4.1
4.1. Analysis
Comparison 4 Six‐dose anti‐VEGF versus four‐dose anti‐VEGF, Outcome 1 Mean change in BCVA at 12 months.
4.2
4.2. Analysis
Comparison 4 Six‐dose anti‐VEGF versus four‐dose anti‐VEGF, Outcome 2 Mean change in CRT at 12 months.
5.1
5.1. Analysis
Comparison 5 50% PDT versus sham treatment, Outcome 1 Mean BCVA at 12 months.
5.2
5.2. Analysis
Comparison 5 50% PDT versus sham treatment, Outcome 2 Recurrence/persistence CSC at 12 months.
5.3
5.3. Analysis
Comparison 5 50% PDT versus sham treatment, Outcome 3 Mean CRT at 12 months.
6.1
6.1. Analysis
Comparison 6 30% PDT versus PDT, Outcome 1 Mean BCVA at 12 months.
6.2
6.2. Analysis
Comparison 6 30% PDT versus PDT, Outcome 2 Recurrence of CSC at 12 months.
6.3
6.3. Analysis
Comparison 6 30% PDT versus PDT, Outcome 3 Mean change in CRT at 12 months.
7.1
7.1. Analysis
Comparison 7 50% PDT versus PDT, Outcome 1 Mean BCVA at 12 months.
7.2
7.2. Analysis
Comparison 7 50% PDT versus PDT, Outcome 2 Recurrence of CSC at 12 months.
7.3
7.3. Analysis
Comparison 7 50% PDT versus PDT, Outcome 3 Mean change in CRT at 12 months.
8.1
8.1. Analysis
Comparison 8 30% PDT versus 50% PDT, Outcome 1 Mean change in BCVA at 12 months.
8.2
8.2. Analysis
Comparison 8 30% PDT versus 50% PDT, Outcome 2 Recurrence of CSC at 12 months.
8.3
8.3. Analysis
Comparison 8 30% PDT versus 50% PDT, Outcome 3 Persistent CSC at 12 months.
8.4
8.4. Analysis
Comparison 8 30% PDT versus 50% PDT, Outcome 4 Mean change in CRT at 12 months.
9.1
9.1. Analysis
Comparison 9 Laser versus observation or sham treatment, Outcome 1 Mean change in BCVA at 12 months.
9.2
9.2. Analysis
Comparison 9 Laser versus observation or sham treatment, Outcome 2 Recurrence of CSC at 12 months.
9.3
9.3. Analysis
Comparison 9 Laser versus observation or sham treatment, Outcome 3 Mean change in CRT at 12 months.
10.1
10.1. Analysis
Comparison 10 Indirect argon laser versus direct argon laser, Outcome 1 Recurrence of CSC at 12 months.
11.1
11.1. Analysis
Comparison 11 Comparison of different laser wavelengths, Outcome 1 Recurrence of CSC at 12 months.
12.1
12.1. Analysis
Comparison 12 Antioxidant supplements versus placebo, Outcome 1 BCVA at 12 months.
12.2
12.2. Analysis
Comparison 12 Antioxidant supplements versus placebo, Outcome 2 Recurrence at 12 months.
12.3
12.3. Analysis
Comparison 12 Antioxidant supplements versus placebo, Outcome 3 Persistence at 12 months.
12.4
12.4. Analysis
Comparison 12 Antioxidant supplements versus placebo, Outcome 4 CRT at 12 months.
13.1
13.1. Analysis
Comparison 13 Beta‐blocker versus placebo, Outcome 1 Mean BCVA at 12 months.
13.2
13.2. Analysis
Comparison 13 Beta‐blocker versus placebo, Outcome 2 Recurrence of CSC at 12 months.
13.3
13.3. Analysis
Comparison 13 Beta‐blocker versus placebo, Outcome 3 BCVA ≥ 20/40 at 12 months.
14.1
14.1. Analysis
Comparison 14 Carbonic anhydrase inhibitors versus placebo, Outcome 1 Recurrent/persistent CSC at 12 months.
15.1
15.1. Analysis
Comparison 15 Helicobacter pylori treatment versus placebo or observation, Outcome 1 Mean BCVA at 12 months.
15.2
15.2. Analysis
Comparison 15 Helicobacter pylori treatment versus placebo or observation, Outcome 2 Persistent CSC at 12 months.
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References to ongoing studies

EUCTR2009‐017959‐98‐NL {unpublished data only}
    1. EUCTR2009‐017959‐98‐NL. Early treatment of patients with central serous retinopathy: a randomized controlled trial ‐ CSR & PDT. apps.who.int/trialsearch/Trial2.aspx?TrialID=EUCTR2009‐017959‐98‐NL (accessed 16 October 2015).
JPRN‐UMIN000005372 {unpublished data only}
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NCT01019668 {unpublished data only}
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NCT01552044 {unpublished data only}
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NCT01630863 {unpublished data only}
    1. NCT01630863. The safe effective light dose of photodynamic therapy for chronic central serous chorioretinopathy. clinicaltrials.gov/ct2/show/NCT01630863 (accessed 16 October 2015).
NCT01797861 {unpublished data only}
    1. Breukink MB, Downes SM, Querques G, Dijk EH, Hollander AI, Blanco‐Garavito R, et al. Comparing half‐dose photodynamic therapy with high‐density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (the PLACE trial): study protocol for a randomized controlled trial. TRIALS 2015;16:419. - PMC - PubMed
    1. NCT01797861. A prospective randomized controlled multicentre trial comparing half‐dose photodynamic therapy (PDT) with high‐density subthreshold micropulse laser treatment in patients with chronic central serous chorioretinopathy (CSC). clinicaltrials.gov/ct2/show/NCT01797861 (accessed 16 October 2015).
NCT01971190 {unpublished data only}
    1. NCT01971190. Efficacy and safety of intravitreal aflibercept injection for subacute central serous chorioretinopathy. clinicaltrials.gov/ct2/show/NCT01971190 (accessed 16 October 2015).
NCT01982383 {unpublished data only}
    1. NCT01982383. A prospective study of the use of micropulse 577nm laser treatment in central serous chorioretinopathy. clinicaltrials.gov/ct2/show/NCT01982383 (accessed 16 October 2015).
NCT01990677 {unpublished data only}
    1. NCT01990677. Eplerenone for the treatment of central serous chorioretinopathy. clinicaltrials.gov/ct2/show/NCT01990677 (accessed 16 October 2015).
NCT02153125 {unpublished data only}
    1. NCT02153125. Eplerenone for the treatment of chronic central serous chorioretinopathy. clinicaltrials.gov/ct2/show/NCT02153125 (accessed 16 October 2015).
NCT02215330 {unpublished data only}
    1. NCT02215330. A randomized, double‐masked, placebo controlled study of the beneficial effects of eplerenone on central serous chorioretinopathy. clinicaltrials.gov/ct2/show/NCT02215330 (accessed 16 October 2015).
NCT02354170 {unpublished data only}
    1. NCT02354170. Short‐term oral mifepristone for central serous chorioretinopathy. A placebo‐controlled dose ranging study of mifepristone in the treatment of CSC (STOMP‐CSC). clinicaltrials.gov/ct2/show/NCT02354170 (accessed 16 October 2015).

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References to other published versions of this review

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