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To compare the anatomical/functional changes after navigated subthreshold pulse laser (SML) and oral eplerenone therapy for chronic central serous chorioretinopathy (cCSC). A total of 36 eyes of 36 patients suffering from cCSC treated with navigated SML (Navilas® 577s; OD-OS GmbH, near Berlin, Germany) (18 eyes, SML group) and oral eplerenone (18 eyes, eplerenone group) were enrolled in this retrospective study. Main outcome measures during a 3-month follow up period included changes of best corrected visual acuity (BCVA), central macular thickness (CMT), foveal subretinal fluid thickness (FSRFT), and subfoveal choroidal thickness (SFCT). At baseline average duration of symptoms was 6.8 ± 0.6 months in SML group and 6.4 ± 0.9 months in eplerenone group (p = 0.127). Mean BCVA, CMT and FSRFT changed significantly over time (p < 0.001). From baseline to 90 days the BCVA improved from 0.3 ± 0.1 to 0.1 ± 0.1 logMAR in SML group and from 0.3 ± 0. to 0.2 ± 0.1 logMAR in eplerenone group, CMT reduced from 357.1 ± 104.3 to 210.6 ± 46.7 μm and from 428.7 ± 107.7 to 332.5 ± 27.5 μm in SML group and eplerenone group respectively, FSRFT reduced from 144.4 ± 108.2 to 22.6 ± 37.2 μm and from 217.1 ± 105.9 to 54.4 ± 86.2 μm in SML group and eplerenone group. 55.6% of patients in SML group and 66.7% in eplerenone group showed a complete resolution of FSRFT during follow up. The interaction between group and time was statistically significant with greater absolute variation for CMT and FSRFT in SML group compared to eplerenone group (p < 0.001 and p = 0.043). SFCT did not change significantly during follow up (p = 0.083) for both groups. Both navigated SML and oral eplerenone were effective treatments showing recovery of retinal morphology and related visual acuity improvement in cCSC. [ABSTRACT FROM AUTHOR]