The occurrence, development and recurrence of CSC may be related to changes in steroid hormone levels caused by mental tension, stress and other factors. Glucocorticoids are closely related to the incidence of CSC6. Studies have reported that there is a simultaneous expression of glucocorticoid receptors (GR), mineralocorticoid receptors (MR) and type 2 hydroxysteroid dehydrogenase (hsd–2) in retinal and choroid tissues, thus demonstrating that the retina and the choroid are novel targets of mineralocorticoids. In rats, the mineralocorticoid receptor specifically binds to aldosterone or high doses of glucocorticoids, and both aldosterone and glucocorticoids can activate receptors and cause the dilation and leakage of the choroid vessels, whereas MR antagonists can reverse these effects2, 7. Therefore, competitive antagonists of the MR are likely to be involved in the pathogenesis of CSC in the choroid. Zhao M. et al.2 have identified that aldosterone upregulates the endothelial vasodilatory potassium channel KCa2.3, which is an endothelial, hyperpolarizing, calcium-dependent channel that is involved in vasorelaxation. This endothelial hyperpolarizing factor pathway is one of the well-known vasorelaxation mechanisms that also occur in large vessels upon aldosterone activation. Mineralocorticoid receptor antagonism reversed the upregulation and activation of this channel-induced vasodilation in the choroid. Interestingly, KCa2.3 is not expressed in retinal vessels but is only expressed in choroid vessels, thus explaining that steroids do not induce vasodilation of the retinal vessels upon MR activation. MR antagonists primarily involve spironolactone and eplerenone, which are primarily used in the treatment of hypertension, aldosteronism and congestive heart failure. The most common side effects are hyperkalemia and low blood pressure. In view of the self-limitation of CSC, MR antagonists are currently used to treat chronic CSC patients. A one-year pilot study by Ghadiali, Quraish MD5 demonstrated that mineralocorticoid antagonists may improve best-corrected visual acuity and decrease subretinal fluid in patients with central serous chorioretinopathy, but these antagonists do not affect the choroidal or macular thicknesses. Nevertheless, the latest results of Sun X, et al.8 suggest that oral spironolactone is a promising treatment for acute CSC because it provides a faster absorption of SRF. Therefore, 75 eyes of 74 patients with chronic CSC were included in this study, and the efficacy
and safety were observed after 8 weeks of treatment with oral spironolactone.
The results of this study demonstrated that SRF was significantly absorbed in chronic CSC patients after 4 weeks of oral spironolactone treatment compared with the baseline SRF, that the best-corrected visual acuity was obviously improved after 4 weeks of treatment compared with the baseline measurement, and that the central macular thickness also exhibited visual reduction on at the end of the 4 weeks of treatment. However, there was no significant difference in the subfoveal choroidal thickness after 4 weeks of oral spironolactone treatment compared with the baseline measurement. At 8 weeks of treatment, the SRF of patients was further absorbed, and both the BCVA and CMT were significantly improved compared with the measurements at previous time points, while the SFCT exhibited no significant difference. No obvious side effects were observed during medication.
A subsequent prospective pilot study by Bousquet et al.3 described 13 patients with CSC who were treated with eplerenone. In their study, visual acuity, central macular thickness and subretinal fluid parameters were measured, and the results showed that eplerenone treatment was associated with a significant reduction in central macular thickness and subretinal fluid level as well as an improvement in visual acuity.
Kapoor KG9 created a retrospective chart review of 32 CSC patients who were treated with spironolactone or eplerenone (50 mg p.o. bid.) or observation, and it was observed that both MR antagonists demonstrated statistically significant visual acuity improvement and subretinal fluid reduction at 1, 2 and 3 months compared to the baseline (p < 0.05). A total of 58.3% of patients had a complete resolution of the subretinal fluid at 2 months of MR antagonist treatment, compared to 12.5% of patients who were under observation (p < 0.05). There was no difference in the efficacy between eplerenone and spironolactone treatments. Spironolactone treatment exhibited increased side effects (8/12 patients, 75%) compared to eplerenone treatment (3/12 patients, 25%; p < 0.05). There is also a study from Herold TR10 that reported that 18 patients with chronic CSC who were treated with 25 mg spironolactone twice daily for 12 weeks exhibited decreases in SRF and CMT as well as improvements in BCVA. These results are similar to our results. However, these research subjects were all foreigners, and our subjects are Chinese. Through our study, we observed that spironolactone treatment is also effective for Chinese people. Additionally, the dose used in our study was 20 mg twice daily, whereas the other study used a dosage of 25 mg twice daily10, which indicates that the low dose is also effective. However, the OCT parameters for subfoveal choroidal thickness did not show significant changes with treatment, although, as previously reported, patients with exudative CSC and subretinal fluids did exhibit significant anatomical improvements. We inferred that perhaps because of the signal loss before the scleral-choroidal edge in some cases, it was difficult to establish clear data on the possible differences in the subfoveal choroidal thickness in intractable chronic CSC patients at baseline and during the follow-up period.
By reviewing the studies of recent years3, 8 4, 10, we observed an interesting result: the absorption of SRF was more obvious after the Chinese studies used MR antagonists than when the European studies used MR antagonists. Sun X, et al.8 demonstrated that complete resolution of SRF was achieved in 55.6% (10/18) of patients, and our research demonstrated that complete resolution was achieved in 29.3% (22/75) of patients, where the patients were Chinese. Herold TR10 reported that the complete regression of subretinal fluid was documented in 25% of the study eyes, and Singh RP4 demonstrated that six eyes (35.3%) within the study demonstrated a complete resolution of SRF upon completion of the treatments. Meanwhile, Bousquet E3 reported that a complete reabsorption of SRF was achieved in 3/12 patients (25%), with those patients being European. Additionally, our study had a larger sample of patients than the previous studies. Although the causes have not yet been thoroughly studied, the differences may be due to changes in hormone levels in stress and the environments; therefore, more clinical studies of multicenter big data are necessary. The limitation of our study was that the follow-up period only consisted of 2 months, which was too short to assess the long-term safety and efficacy of MR antagonism for the treatment of intractable chronic CSC and the recurrence rates. Larger, prospective, randomized controlled clinical trials should be further investigated, with longer follow-up periods.