The study is a prospective, randomized, placebo-controlled study for high-dose oral antioxidants for patients who presented with acute CSC between December 2004 and December 2008 at the Retina Unit, Prince of Songkla University, Thailand. The research was approved by the Ethics Committee, Faculty of Medicine, Prince of Songkla University in December 2004 (EC 47/362-023), and before the enrollment all patients signed the consent forms. The patients were randomly assigned to high-dose antioxidant or placebo drugs. The randomization was computer generated with a 1:1 ratio, block lengths of 4 and random numbers were coded to all bottles. Moreover, the codes were in envelops until the end of the study. The inclusion criteria were patients with acute CSC (within 6
weeks of onset), aged between 30–50
years, new or recurrent attack (symptom-free 6
months or longer), a fluorescein angiography (FA) confirmed diagnosis with inkblot (Figure ) or smokestack leakage, an optical coherence tomography (OCT) by Stratus OCT™ (Carl Zeiss Meditec, Inc., Dublin, CA) showing definite subretinal fluid and the patients’ ability for proper follow-up. The exclusion criteria were chronic CSC (longer than 6
weeks), multiple attacks (more than 2 times), large pigment epithelial detachment (more than 1 disc diameter), multiple pigment epithelial detachment or diffuse retinal pigment epitheliopathy, younger or older ages, a follow-up time less than 3
months, a complicated CSC such as secondary choroidal neovascularization detected from FA, pregnancy, steroid use and patients with contraindication for high-dose antioxidants therapy such as heavy smokers, those with lung cancer, thyrotoxicosis, renal stones and anemia (hematocrit less than 30%).
The patient with central serous chorioretinopathy showed typical inkblot leakage in the early phase (left) and late phase (right) from fluorescein angiography.
The study group (group A) received high-dose antioxidant tablets (IcapsTM
, Alcon Laboratories) that contained vitamin A (6600
IU), vitamin C (400
mg), vitamin E (150
IU), riboflavin (10
mg), zinc (60
mg), copper (4
mg), selenium (40
mg), manganese (4
mg) and lutein/zeaxanthin (4000 micrograms). The drug was taken immediately after diagnosis, 1 tablet two times a day after meals for 3
months or until the complete resolution of subretinal fluid as assessed by OCT.
The control group (group B) received placebo tablets that were specially made for the study and were identical to the study tablets in their size, color and identification name and were taken in similar ways as the study drugs. Both drugs were also in identical opaque bottles and prepared by one non-clinician research assistant.
The study was an intention-to-treat analysis and there was no cross-over of patients between the groups after the study. The corresponding author (M.R.) generated the allocation sequence, enrolled the patients and assigned patients to any additional treatments when needed.
The patients were scheduled for follow-up every month. The visual acuity (VA), using the logarithm of minimum angle of resolution (logMAR), OCT using central macular thickness (CMT), FA and any complications were assessed during each visit. The study drug or placebo drug was discontinued in a patient when OCT demonstrated complete resolution of subretinal fluid or at the end of the 3rd
month after finishing 3 bottles of the drug. After 3
months, additional treatments such as laser photocoagulation for extrafoveal leakage or PDT for juxtafoveal or subfoveal leakage were considered for any persistent FA leakage (Figure ).
The primary outcomes were the changes in VA and CMT recorded by OCT during every visit. The secondary outcomes were the number of patients with subretinal fluid at each follow-up time, the number of patients who showed FA leakage at the end of the 3rd month and patients who received additional treatments in each group.
The sample size was calculated with α
0.05 (two-sided), β
0.2 and determined to be approximately 24 patients in each group. Assuming an expected dropout rate of 20%, 29 patients in each group were needed. An independent t
-test was used for parametric data. The chi-square and Mann Whitney U
-test were used for non-parametric data. A p-value less than 0.05 was considered significant.