ABSTRACT

Central serous chorioretinopathy (CSCR) is the second most common maculopathy after diabetic maculopathy between the third and fifth decades of life. CSCR is characterized by serous neurosensory retinal detachment occasionally coexisting with retinal pigment epithelium (RPE) detachment. CSCR usually has good clinical prognosis, often resolving spontaneously within the first three months. However, some patients may have recurrent episodes and chronic disease. CSCR can cause permanent visual loss due to persistent neurosensory retinal detachment and RPE atrophy, especially in chronic cases. In recent years, verteporfin-photodynamic therapy applied with standard and low-dose/low-fluence protocols, anti-vascular endothelial growth factors, glucocorticoid antagonists, mineralocorticoid receptor antagonists, and subthreshold micropulse laser with varying parameters have been investigated as treatment options. In this review, we evaluated randomized and non-randomized case series conducted after 2000 that included at least 3 patients with chronic CSCR over 3 months in duration who were treated with current treatment options for chronic CSCR.

Introduction

Central serous chorioretinopathy (CSCR) is characterized by serous neurosensory retinal detachment (NSD) accompanied by retinal pigment epithelium (RPE) detachment in some cases, and is the second most common maculopathy after diabetic maculopathy between the third and fifth decades of life.^1,2,3 Clinically, CSCR has a good prognosis and usually resolves spontaneously within the first 3 months.^2,3 However, approximately 5% of cases can become chronic.^1,4 Refractory NSD, which can develop in chronic CSCR, may lead to photoreceptor damage, diffuse RPE changes, RPE atrophy, and subsequent permanent vision loss.^1,2,3

Studies on the subject have demonstrated that the two main factors involved in the pathogenesis of CSCR. The first is alterations in the autoregulatory mechanisms of choroidal circulation and the subsequent choroidal ischemia, and the second is irregularities in RPE pump function.^5,6,7 Choroidal stasis, inflammation, and ischemia due to dysregulation of regulatory proteins (glucocorticoids, mineralocorticoids, epinephrine, norepinephrine) in the choroidal circulation leads to an increase in choroidal permeability.^7,8,9,10 This hypothesis is corroborated by the presence of local and/or diffuse leakage in fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA), which are important diagnostic methods for CSCR.^{5,10,11,12,13} Due to the multifactorial and complex mechanism of CSCR pathophysiology, several treatment options, such as conventional laser (CL) and verteporfin photodynamic therapy (PDT) have been tried, particularly in the treatment of the chronic type; however, CL was reported to have no significant effect on the final visual acuity or recurrence rate and to have toxic effect on the RPE and photoreceptors.^14,15 Although successful results were obtained with the standard protocol (full-dose, full-fluence) PDT (SP-PDT), this treatment was also observed to have toxic effects on the RPE and photoreceptors.^16,17,18 The adverse effects of CL and SP-PDT have prompted studies in recent years on the safety and efficacy of subthreshold micropulse laser (SML), verteporfin PDT with different parameters (half-dose [HD] or half-fluence [HF]), glucocorticoid antagonists, mineralocorticoid receptor (MR) antagonists, and anti-VEGF agents (Figure 1).^19,20,21,22

This review evaluated current treatment approaches to chronic CSCR based on randomized and nonrandomized studies that accepted symptom duration of at least 3 months as chronic disease and included at least a case series (more than 3 cases).

Conclusion

An evaluation of the literature data regarding current treatment options for chronic CSCR, such as SML, anti-VEGF, MR antagonists, and PDT, suggests that SML is superior to CL in terms of adverse effects and comparable to PDT in terms of efficacy. Assessing the effectiveness of SML using longer-term follow-up data will provide more reliable information for comparison with the effectiveness of PDT. In addition, similar to CL, the ineffectiveness of SML in diffuse RPE leakages is considered an additional disadvantage. Although the valuable prospective randomized study by Artunay et al.²² offered promising results, studies on anti-VEGF have usually been reports of a few cases, which limits the power of these studies. Therefore, performing randomized studies with larger sample sizes will yield more reliable results. Moreover, the most probable pathogenesis of the disease is not closely related to the mechanism of action of anti-VEGF, which suggests that these agents may not be very effective. Studies on MR antagonists have shown that these are effective treatment options; however, the results indicate that these short acting agents are more disadvantageous in terms of patient compliance and in comparison with treatment options with more permanent effects such as PDT and SML. Studies with longer follow-up will also provide more definitive data regarding the effectiveness of MR antagonists. Finally, although PDT is known to be more costly than CL, studies indicate that verteporfin PDT is superior to and safer than CL therapy in terms of effectiveness and adverse event profiles, particularly in chronic, subfoveal, and juxtafoveal involvement. In particular, the fact that PDT at different parameters (HD-PDT, HF-PDT) minimized adverse effects such as choroidal ischemia and CNV supports this treatment as an effective and safe treatment option for chronic CSCR.