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Giacomo Boscia,1,&ast; Pasquale Viggiano,1,&ast; Federica Marzulli,1 Maria Oliva Grassi,1 Pasquale Puzo,1 Stefano Dore,2 Antonio Pinna,2 Giovanni Alessio,1 Francesco Boscia1 1Department of Translational Biomedicine Neuroscience, University of Bari “Aldo Moro”, Bari, Italy; 2Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy&ast;These authors contributed equally to this workCorrespondence: Pasquale Viggiano, Department of Translational Biomedicine Neuroscience, University of Bari “Aldo Moro”, Piazza Giulio Cesare, 11, Bari, Italy, Tel +390805593728, Email pasquale.viggiano90@gmail.comPurpose: To assess the long-term morpho-functional retinal and choroidal changes in chronic central serous chorioretinopathy (cCSC) pachychoroid eyes in response to continuous oral eplerenone (EPL) treatment.Methods: This pilot study was conducted on patients with unilateral exudative cCSC. We enrolled a total of 17 exudative cCSC and 17 non-exudative fellow eyes of 17 patients. Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography [OCT] and OCT angiography) parameters in both eyes were collected at baseline. Follow-up data were collected at 6, 12, and 48 months after initiation of EPL treatment.Results: (i) Exudative cCSC eyes: Compared with baseline (0.34± 0.13 LogMAR), BCVA significantly improved at follow-up examinations (6 months: 0.28± 0.13 LogMAR, p=0.039; 12 months: 0.22± 0.11 LogMAR, p=0.025; 48 months: 0.21± 0.08 LogMAR, p=0.028). Furthermore, there was a significant reduction from baseline in all structural OCT parameters (subretinal fluid and subfoveal choroidal thickness [SFCT]; p< 0.05). (ii) Non-exudative fellow eyes: There was no significant change in BCVA. There was a significant reduction from baseline in SFCT and choriocapillaris flow deficit percentage (p< 0.05).Conclusion: In this pilot study, continuous oral EPL therapy in cCSC pachychoroid eyes resulted in