Effects of Ketoconazole on the Clinical Recovery in Central Serous Chorioretinopathy

Abstract

Purpose: Patients with hypercortisolism have been associated with a higher prevalence of the pachychoroid spectrum including central serous chorioretinopathy (CSCR), which may explain the inconsistency of therapeutic responses of the mineralocorticoid receptor antagonist because hyperaldosteronism has rarely been detected in patients with CSCR. Therefore, this study aimed to evaluate the effects of ketoconazole, the first-line cortisol inhibitor, on the resolution of subretinal fluid (SRF) in CSCR and to analyze correlations between choroidal thickness and steroid hormones.

Patients and methods: This retrospective cohort study included 41 naïve CSCR eyes of 41 patients categorized into control (20 eyes) and treatment (21 eyes) groups. Patients in the treatment group were administered oral ketoconazole at a daily dose of 400 or 600 mg for 3-6 weeks. At week 12, rescue laser therapy was applied to patients exhibiting persistent SRF. Thus, a survival analysis was performed to determine the time interval from presentation to clinical resolution of SRF. Secondary outcomes consisted of eyes with persistent SRF and factors affecting the therapeutic response.

Results: The mean 24-hour urinary free cortisol (UFC) levels were elevated at 181 ± 70 and 150 ± 68 µg/day (range: 20-150) in the treatment and control groups, respectively (p = 0.21). After controlling for age and gender, baseline UFC levels were significantly associated with choroidal thickness in both eyes (p < 0.05). Ketoconazole significantly increased the CSCR resolution with the median time to resolution of 7 vs 16 weeks (p < 0.01) and decreased the proportion of eyes receiving rescue therapy at 12 weeks (23.8% vs 50%; p = 0.01). Prolonged CSCR durations were likely found in elderly patients with thick choroids in fellow eyes.

Conclusion: Patients with CSCR showed elevated glucocorticoids, which further correlated with their choroidal thickness. Using cortisol blockers may shorten the duration of existing SRF.

Keywords: choroidal thickness; cortisol; mineralocorticoid receptor antagonist; pachychoroidopathy.

Figure 1

The correlations between choroidal thickness and free cortisol levels. The scatter plots of all study eyes show a significant linear association between 24-hour urinary free cortisol levels and subfoveal choroidal thickness in eyes with central serous chorioretinopathy (A) and fellow eyes (B).

Figure 2

Kaplan–Meier survival estimates of time to complete resolution of central serous chorioretinopathy. These plots indicate that the median time to complete subretinal fluid absorption was 7 weeks in the ketoconazole-treated group, and 16 weeks in the control group (p = 0.01, Log rank test).

Figure 3

A chronic central serous chorioretinopathy (CSCR) patient who was later diagnosed with obstructive sleep apnea. (A and B) A 54-year-old obese man had been diagnosed with CSCR in the right eye for 6 months before the presentation. The presenting 24-hour urinary free cortisol (UFC) was 190 µg/day. (C and D) After receiving a 6-week course of ketoconazole, the choroidal thickness gradually decreased, (E) and CSCR resolved at 10 weeks post-treatment (UFC = 90 µg/day). (F) Six months later, CSCR recurred; the sleep laboratory revealed 34 episodes of apnea per hour. (G) The macula was dry after 6 weeks of airway ventilation therapy.

Figure 4

A patient with high-risk features for persistent central serous chorioretinopathy (CSCR). (A and B) A 51-year-old man was referred to our hospital because of an 18-week history of persistent CSCR in the left eye (OS). He discontinued using nasal steroids at least 8 weeks prior to the referral. Fluorescein angiogram demonstrated multiple spots of leakage hyperfluorescence in the superonasal macula. (C) He received a 6-week course of 400 mg/day ketoconazole, which resulted in resolution of CSCR at 7 weeks visit. (D) Baseline subfoveal choroidal thickness in the right eye was thicker than that in OS (459 and 398 µm).