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PURPOSE To quantitatively evaluate the photoreceptor structural changes in the fellow unaffected eyes of patients with unilateral central serous chorioretinopathy (CSC). METHODS This is a retrospective cross-sectional study. We analyzed data from patients with diagnosis of unilateral CSC, as based on clinical examination and multimodal imaging, who had structural optical coherence tomography obtained. An additional group of age-matched healthy patients was included for comparison. Main outcome measures were as follows: (1) the foveal photoreceptor outer segment lateral surface and (2) the foveal choroidal thickness. RESULTS One hundred and sixty fellow unaffected eyes of 160 unilateral CSC patients and 50 age-matched controls (50 eyes) were included. The mean ± SD age was 51.6 ± 11.1 years (range 28-80 years) in the unilateral CSC group and 52.8 ± 10.8 years (range 31-74 years) in the control group (P = 0.511). The foveal photoreceptor outer segment lateral surface was significantly increased in the unaffected eyes with CSC in the fellow eye (0.068 ± 0.007 mm) as compared with control eyes (0.060 ± 0.005 mm, P < 0.0001). The mean ± SD foveal choroidal thickness was 368.0 ± 105.7 µm in the unilateral CSC group and 302.9 ± 92.2 µm in control patients (P < 0.0001). In the Pearson correlation test, the photoreceptor outer segment lateral surface correlated with the choroidal thickness in the CSC group (R = 0.166, P = 0.016) but not in the control group (R = -0.025, P = 0.864). CONCLUSION Our results corroborate the hypothesis that retinal and choroidal changes affect both eyes of patients with acute/history of unilateral disease. These structural changes could be intended as an imaging evidence of reduced photoreceptor outer segment turnover secondary to retinal pigment epithelium and choroid dysfunction.