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Treatment of chronic central serous chorioretinopathy (cCSC) remains a topic of controversy. As cCSC is a disease that can wax and wane, treatment efficacy is difficult to assess especially when trials compare active treatments without any placebo/control group. In this study, we systematically reviewed short‐term efficacies of any cCSC treatment tested in randomized controlled trials (RCT) and employed network meta‐analyses to compare to non‐treatment controls. We searched 11 literature databases on 20 March 2022 for RCTs of treatment of cCSC. We identified 17 RCTs including a total of 1172 eyes. Treatments included conventional laser (44 eyes), half‐dose or half‐fluence photodynamic therapy (PDT) (298 eyes), ranibizumab (16 eyes), antioxidants (50 eyes), mineralocorticoid receptor antagonists (187 eyes), rifampicin (91 eyes), selective retina therapy (SRT) (67 eyes) and subthreshold micropulse laser (192 eyes). Compared with controls, significant benefit on complete subretinal fluid resolution was only obtained from half‐dose or half‐fluence PDT (OR: 20.6; 95% CI: 6.3–66.7; p < 0.0001) and conventional laser (OR: 36.4; 95% CI: 2.0–655.7; p = 0.015), and at an order of magnitude lower degree from SRT (OR: 3.4; 95% CI: 1.7–6.8; p = 0.00075). Compared with controls and after sensitivity analyses, significant benefit in the change in best‐corrected visual acuity was only obtained by half‐dose/‐fluence PDT (−0.13 logMAR; 95% CI: −0.20 to −0.06 logMAR; p = 0.00021). In conclusion, three treatment options provide significant improvement over no treatment: half‐dose/‐fluence PDT, conventional laser and to a much lesser degree SRT. Considering that conventional laser can only be applied for extrafoveal leaks, and the long‐term data available for PDT‐based treatments finding persisting treatment results, half‐dose or half‐fluence PDT is the only viable treatment option for patients with cCSC. Shortage issues with verteporfin should not lead to employment of ineffective treatment modalities, as they put patients at unnecessary risk of adverse events.

Supplemental Digital Content is Available in the Text.None of the chronic central serous chorioretinopathy patients who received a single treatment with fovea-involving half-dose photodynamic therapy in two randomized clinical trials showed signs of developing foveal atrophy after treatment. This adds to the evidence that half-dose photodynamic therapy is a safe long-term treatment for chronic central serous chorioretinopathy patients.

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Half-dose photodynamic therapy leads to a significantly larger decrease in the height of the highest macular pigment epithelial detachment compared with high-density subthreshold micropulse laser treatment in chronic central serous chorioretinopathy.