Clinical efficacy and mechanistic evaluation of Eplerenone for central serous chorio-retinopathy – the VICI randomised trial

INTERVENTION: Patients who consent will be randomised using an online system to active drug (Eplerenone) or placebo. They will be given a 25‐mg dose (tablet form) for 1 week, reviewed and if tolerated the dose will be increased to 50 mg. They will be reviewed again at 4 weeks and then every 3 months for a year. Their vision will be assessed using visual acuity (letter charts) and specialised ophthalmic imaging, as well as quality of life questionnaires at the start and the end of the study. Treatment will be stopped at week 4, months 3, 6, 9 or 12 if there is complete resolution of sub‐retinal fluid (SRF) under the fovea in the study eye. Treatment will be restarted at a subsequent visit if there is recurrence of sub‐foveal SRF. The same dose escalation process will apply on restarting treatment. Treatment will be stopped for individual patients if they develop a complication of taking eplerenone. Also if at any of study visits visual acuity drops by 15 or more letters, the ophthalmologist may consider alternative therapies and may decide to stop the study intervention. CONDITION: Specialty: Ophthalmology, Primary sub‐specialty: Glaucoma; UKCRC code/ Disease: Eye/ Disorders of choroid and retina ; Eye Diseases ; Central serous chorio‐retinopathy PRIMARY OUTCOME: Primary outcome as of 23/01/2017:; Best Corrected Visual Acuity measured using validated ETDRS vision charts, at the 12 month visit, adjusted for baseline BCVA.; ; Original primary outcome:; The change in Best Corrected Visual Acuity measured using validated ETDRS vision testing at baseline, 4 weeks, 3, 6, 9 and 12 months. INCLUSION CRITERIA: Inclusion criteria as of 12/01/2017: 1. Aged between 18 and 60 years 2. Visual impairment due to CSCR of = 4 months duration defined as: 2.1. Subfoveal presence of SRF on OCT AND 2.2. Characteristic appearance of CSCR on FFA and Indocyanine‐green angiography (ICGA). AND 2.3. Investigator believes that there is sufficient evidence from patient history, case note documentation or appearance of the macula that CSCR has been present for at least 4 months 3. Women must be willing to use effective contraception, be surgically sterile or post‐menopausal for >12 months 4. Able to provide written informed consent The following additional inclusions apply to a study eye only (i.e. they may be present for a non‐study eye): 1. A study eye should have an Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA score greater than 53 letters and less than 86 letters 2. A study eye should have clear ocular media and adequate pupillary dilatat SECONDARY OUTCOME: Secondary outcomes as of 12/01/2017:; 1. Low luminance visual acuity is measured immediately after measuring BCVA at baseline, 4 weeks, 3, 6, 9 and 12 months by adding a 2 log neutral density filter and recording the number of letters read; 2. Central subfield retinal thickness (CSRT) as measured by optical coherence tomography (OCT) estimated at 12 months, including CSRT measured at interim visits and adjusted for baseline CSRT; 3. Change in sub‐retinal fluid (SRF)thickness as measured by OCT at 12 months; 4. Systemic and ocular adverse events at any time during the 12 month follow‐up period; 5. Proportion of patients with macular atrophy of the Retinal pigment epithelium (RPE) defined as hypoautofluorescence at 12 months; 6. Area change in macular RPE hypoautofluorescence at 12 months; 7. Choroidal thickness as measured by enhanced depth imaging OCT at 12 months, adjusted for baseline choroidal thickness; 8. Proportion of patients with reduced choroidal permeability on Indocyanine green angiography at 12 months; 9. Time to resolution of SRF as measured by OCT at 4 weeks, 3, 6, 9 and 12 months; 10. Proportion of patients with complete resolution of SRF at each time point of the study; 11. Patient‐reported visual function using Visual Function Questionnaire VFQ 25 will be assessed at baseline and 12 months; 12. Classification of all study eyes as complete, partial or no resolution of SRF at each time point of the study. Partial resolution of SRF is defined as a decrease of >25 % of CMT from baseline due to resolution of SRF. A non‐responder is defined as having an increase in SRF or decrease in SRF =25% from baseline. Recurrence will be defined as the appearance of new SRF in a study eye after complete resolution of SRF at any point. ; 13. Classification of all study eyes by each FFA phenotype, such as smoke stack, ink‐blot and chronic epitheliopathy, is assessed at baseline; 14. Classification of all study eyes as early, late, or non responder. An early responder is defined as complete or partial resolution of sub‐foveal SRF by 3 months. A late responder is defined as complete or partial resolution of sub‐foveal SRF after 6 months; 15. Incidence of CSCR in the fellow eye as measured by OCT, FFA, ICGA or AF at baseline, 4 weeks, 3, 6, 9 and 12 months; ; Original secondary outcomes:; 1. Low luminance visual acuity is measured immediately after measuring BCVA at baseline, 4 weeks, 3, 6, 9 and 12 months by adding a 2 log neutral density filter and recording the number of letters read; 2. Central subfield retinal thickness (CSRT) as measured by optical coherence tomography (OCT) estimated at 12 months, including CSRT measured at interim visits and adjusted for baseline CSRT; 3. Change in sub‐retinal fluid (SRF) volume as measured by OCT at 12 months; 4. Systemic and ocular adverse events at any time during the 12 month follow‐up period; 5. Proportion of patients with macular atrophy of the Retinal pigment epithelium (RPE) defined as hypoautofluorescence at 12 months; 6. Area change in macular RPE hypoautofluorescence at 12 months; 7. Choroidal thickness as measured by enhanced depth imaging OCT at 12 months, adjusted for baseline choroidal thickness; 8. Proportion of patients with reduced choroidal permeability on Indocyanine green angiography at 12 months; 9. Time to resolution of SRF as measured by OCT at 4 weeks, 3, 6, 9 and 12 months; 10. Proportion of patients with complete resolution of SRF at each time point of the study; 11. Patient‐reported visual function using Visual Function Questionnaire VFQ 25 will be assessed at baseline and 12 months; 12. Correlation of final visual acuity (12 months) with age of patient; 13. Correlation of presence of granular/confluent hypoautofluorescence in macula with final visual acuity at 12 months; 14. Proportion of each Fundus Fluorescein angiogram phenotype such as smoke stack, ink‐blot and chronic epitheliopathy at 12 months