PurposeTo identify predictive biomarkers of treatment outcomes by multimodal retinal imaging in patients affected by central serous chorioretinopathy (CSC).Patients and methodsIn this interventional non-randomized clinical study, 27 treatment-naive CSC patients were prospectively enrolled and treated with oral eplerenone for 5-13 weeks. Primary outcomes included presence of pathological findings on indocyaine green angiography (ICGA), structural optical coherence tomography (OCT) and OCT-angiography (OCT-A) at baseline associated with different response to the treatment.ResultsA total of 29 eyes of 27 patients (2 females, 25 males) met the inclusion criteria and were included in the study (mean age was 45±7 years). Mean CSC duration at baseline was 13.5±4.4 weeks. After a mean of 10.5 weeks of treatment, mean central macular thickness significantly reduced (P<0.001), and mean best-corrected visual acuity improved (P<0.001). Seventeen eyes (61%) demonstrated total reabsorption of subretinal fluid on structural OCT, five eyes (18%) presented a partial response to eplerenone therapy and six eyes (21%) showed no response. The complete response to the treatment was associated with absence of CNV at OCT-A and the presence of hotspot at ICGA (P<0.001 and P=0.002, respectively). None of eight eyes with CNV in OCT-A imaging had a complete response to eplerenone and none of three eyes without hotspot at ICGA showed a complete response to the treatment.ConclusionsMultimodal retinal imaging allowed us to propose predictive biomarkers (ie, absence of CNV on OCT-A and presence of hotspot on ICGA) for treatment outcomes.