In a prospective proof-of-concept study probing the role of para-inflammation in central serous chorioretinopathy (CSC) pathogenesis, eligible subjects with chronic CSC non-responsive to conventional treatment received a single dexamethasone (DEX) implant monotherapy. Six middle-aged males (mean age = 46.5 ± 10.8 years) with a mean disease duration of 4.5 ± 2.5 years, at the primary efficacy endpoint of six weeks, showed complete resolution of subretinal fluid (SRF) in four out of six eyes, significant reduction of SRF height (174 ± 86 μm to 22 ± 34 μm; P = 0.028) and central subfield thickness (347 ± 139 μm to 180 ± 47 μm; P = 0.003), indicating DEX as a promising treatment option for chronic CSC.