Reduced-fluence photodynamic therapy versus placebo for central serous chorioretinopathy (REPLAY trial): rationale and study protocol of a pivotal double-blind randomised controlled trial

Introduction Chronic central serous chorioretinopathy (CSC) can cause progressive and permanent vision loss. Although photodynamic therapy (PDT) is a primary treatment option globally, it is not approved for CSC worldwide, limiting therapeutic access.

The REPLAY trial is a phase III, investigator-initiated trial to evaluate the efficacy and safety of reduced-fluence PDT (rf-PDT) for chronic CSC to seek the first regulatory approval globally. Methods and analysis This study comprises two cohorts.

The 'untreated cohort' is a multicentre, randomised, placebo-controlled, double-masked trial involving 60 patients with untreated, fovea-involving chronic CSC, randomised 2:1 to receive a single rf-PDT or placebo treatment. The 'previously treated cohort' is a single-arm, open-label trial for up to 10 patients with recurrent CSC after PDT.

The primary endpoint for both cohorts is the proportion of eyes with a complete resolution of subfoveal fluid at 12 weeks post-treatment, assessed by optical coherence tomography. Secondary endpoints include changes in best-corrected visual acuity, central choroidal thickness, recurrence rates and incidence of adverse events over a 48 week follow-up.