Eplerenone, a drug used for people with central serous chorioretinopathy, is no more effective than placebo. Neither visual acuity nor the build-up of fluid in the eye shows an important improvement.
Central serous chorioretinopathy is a serious eye condition that causes blurred and distorted vision. Fluid collects underneath the macula, which is the central area of the retina. The condition mostly affects men aged 20–45 years, although it can affect women too. A specific cause is rarely identified.
This NIHR-funded trial is the biggest and most robust one to date that investigates the use of eplerenone for this condition. Results confirm that the drug used for the condition is unlikely to lead to important benefits.
Why was this study needed?
Central serous chorioretinopathy (CSC) usually occurs in one eye. For most people, it gets better by itself within four to six months, without any long-term changes to vision. However, for a small number of people, it can become a long-term problem. For these people, the retina can be damaged by prolonged swelling and lead to loss of sight.
Treatment is usually recommended if the condition lasts longer than six months. Treatment options include thermal laser or photodynamic therapy. There is little current evidence about the effectiveness of alternative drug treatments.
Before this trial, the authors had identified a few small (phase 1) studies of aflibercept, photodynamic laser therapy and eplerenone, but these were statistically underpowered. This means that they had too few participants to be reliable.
This trial, the first randomised superiority trial of its kind, was designed to improve the quality and certainty of evidence and aimed to recruit a sample of 104 patients from 22 UK NHS hospitals.
What did this study do?
On completion, this randomised controlled trial had recruited 114 adults from 22 hospitals in the UK. Patients enrolled had CSC for at least four months, without any previous treatment. In one group, 57 patients were given eplerenone tablets for up to 12 months, alongside usual care. They took 25mg per day for a week, increasing to 50mg per day if their potassium levels were normal. The other 57 patients were given identical-looking placebo tablets for up to 12 months alongside usual care. All patients were followed up after one week, and after one, three, six, nine and 12 months.
No patients, clinicians or people assessing the outcomes knew which group anyone was in.
Visual acuity was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts. These charts have five letters on each line, and the authors specified a clinically important difference or gain in acuity as more than five letters (or one line) on these charts.
This trial was well conducted and the number of participants was sufficient to have found a clinically meaningful difference between the groups if one existed.
What did it find?
- Best-corrected visual acuity (BCVA) was measured by accredited optometrists using the acuity charts. Mean acuity at 12 months in the eplerenone group was 80.4 letters, and in the placebo group was 79.5 letters (estimated mean difference 1.73 letters, 95% confidence interval -1.12 to 4.57). There was, therefore, no clinically important or statistically significant difference in BCVA between the groups at 12 months.
- Other outcomes were measured at 12 months, such as subretinal fluid thickness, the average time until the fluid was reabsorbed, and the average time to recurrence of the fluid. None of these showed any significant differences between the groups in favour of eplerenone either.
- There were no serious adverse events in the eplerenone group. The placebo group reported three serious adverse events, none of which were associated with the placebo tablet. Eight people in each group had to stop their trial tablet due to increased potassium levels.
What does current guidance say on this issue?
There are no national guidelines on the treatment of CSC. Moorfields Eye Hospital NHS Foundation Trust in London has produced a patient information leaflet on the condition. This lists oral medications such as eplerenone as treatment options but highlights that further research is being carried out to evaluate these drugs.
Eplerenone is not currently licensed for treating this condition in the UK.
What are the implications?
This trial has provided good evidence that Eplerenone has little or no meaningful benefit when used to treat patients who have lived with CSC for longer than four months. As such, the search for other treatments can continue.
This trial reinforces the value of well-conducted large trial trials in answering important questions faced by ophthalmologists in practice.
Citation and Funding
Lotery A, Sivaprasad S, O’Connell A et al. Eplerenone for chronic central serous chorioretinopathy in patients with active, previously untreated disease for more than 4 months (VICI): a randomised, double-blind, placebo-controlled trial. Lancet. 2020;395:294-303.
This project was funded by the Efficacy and Mechanism Evaluation Programme (project number 13/94/15), which is a Medical Research Council and National Institute for Health Research partnership.
BNF. Eplerenone. London: BMJ Group and Pharmaceutical Press; 2020.
Khan Y, Mapani A, Islam N, Tufail A. Patient information: central serous chorio-retinopathy (CSCR). London: Moorfields Eye Hospital NHS Foundation Trust; 2018.
Lowth, M. Macular disorders. Leeds: Patient; 2019.
RNIB. Central serous retinopathy. London: Royal National Institute of Blind People. [Accessed on 25 March 2020].
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre