This article is more than 5 years old. Information may no longer be current.
BLOG: How do eplerenone and spironolactone treat CSCR?
Click Here to Manage Email Alerts
In December, Primary Care Optometry News quoted me in an article about central serous chorioretinopathy. The article talked about a lot of facets of the disease, and one of them was a new oral treatment with eplerenone.
This is a fairly new treatment, and since the article ran I’ve gotten some good questions and comments from eye doctors who read it and were curious about it. So, I wanted to use this month’s post to dig deeper into this medication and how it works for treating central serous chorioretinopathy (CSCR).
There are actually two meds discussed in the literature for CSCR: spironolactone and eplerenone. Both are most commonly prescribed for hypertension and congestive heart failure. We’ll go into their differences later, but both drugs are mineralocorticoid receptor antagonists. Before we go into how they work for CSCR, let’s review how this drug class works.
Our adrenal glands secrete three types of corticosteroids: glucocorticoids, mineralocorticoids and androgens. They’re called corticosteroids because they’re produced in the cortex of the adrenal, as opposed to adrenaline and noradrenaline produced in the medulla of the adrenal.
The main job of the first type of corticosteroids, glucocorticoids, is to raise blood sugar by glucose metabolism. But they have a major secondary function, which is to decrease inflammation. The primary glucocorticoid in the body is cortisol, and common glucocorticoid medications are prednisone and dexamethasone.
The second type of corticosteroids are mineralocorticoids, and these are primarily used for sodium and water transport. They help reabsorb sodium in the kidneys, also reabsorbing water and, thus, acting to increase blood pressure. They also have a secondary effect to decrease inflammation. The primary mineralocorticoid in the body is aldosterone, and the most common mineralocorticoid medication is fludrocortisone.
The third and final type of corticosteroids are androgens, such as testosterone. We dug deeper into androgens 2 years ago, so we’ll leave those alone for now.
The causes of CSCR are multiple and complicated, but certainly the intake of steroids has been proven many times over as an independent risk factor for CSCR, whether oral, IV, inhaled or intranasal. Most glucocorticoids exert their effects on the body by binding to glucocorticoid receptors (GRs), but they can also bind to mineralocorticoid receptors (MRs). Most of the MRs in the body are in the kidney, but there are also MRs in the retina, retinal pigment epithelium (RPE) and choroid. Given that mineralocorticoids play a role in sodium pump function and fluid retention, it’s not a far leap to see how excess MR stimulation would lead to a hyperpermeability in the choroid and subretinal fluid above the pumps of the RPE. And this has been shown in rats: Zhao and colleagues demonstrated that mineralocorticoid activation in rat eyes via aldosterone induced choroidal vessel dilation and leakage, similar to that seen in human cases of CSCR.
This brings us back to our two meds for CSCR: spironolactone and eplerenone. These meds are MR blockers. This explains why they work to lower blood pressure, given mineralocorticoids work to increase blood pressure, but it also explains why they might help the fluid accumulation in CSCR.
But what’s the difference between the two? Spironolactone works a lot better to antagonize MRs and stop fluid egress, but it also has more side effects. It has a higher affinity for the receptors of all corticosteroids (including androgens), so increased levels of this drug can cause sexual side effects like gynecomastia, decreased libido, menstrual irregularities and erectile dysfunction. Eplerenone is a spironolactone derivative, so it selectively binds to MRs while minimizing binding to glucocorticoid, androgen and progesterone receptors; thus, there is no documented sexual side effects with eplerenone. That’s the positive news for eplerenone, but the drawback is that its affinity to MRs is approximately 20 times less than spironolactone. Both drugs can cause hyperkalemia.
What does the literature say? Do these drugs work? A PubMed search shows 16 peer-reviewed publications (all within the last 5 years) that studied this question, but most of these were retrospective case reports or case series. Four were prospective studies (Rahimy et al., Bousquet et al. 2015, Bousquet et al. 2013, Herold et al.), and each one found improvement in things like foveal thickness, subretinal fluid height and/or choroidal thickness. I won’t summarize each study, but I encourage you to read them for yourself if you’re curious. More work needs to be done to determine the best doses and duration of the treatment. And although nearly all studies found some kind of anatomical improvement, it doesn’t necessarily mean that will translate to improved visual acuity.
Although MR-antagonists are not yet accepted as standard of care treatment for CSCR, we may be at the start of a new option for these patients, and it’s something to look out for in the future.
References:
Bousquet E, et al. Retina. 2013;doi:10.1097/IAE.0b013e318297a07a.
Bousquet E, et al. Retina. 2015;doi:10.1097/IAE.0000000000000614.
Haimovici R, et al. Ophthalmology. 2004;doi:10.1016/j.ophtha.2003.09.024.
Herold TR, et al. Graefes Arch Clin Exp Ophthalmol. 2014;doi:10.1007/s00417-014-2780-6.
Kleinberger AJ, et al. Laryngoscope. 2011;doi:10.1002/lary.21967.
Rahimy E, et al. Retina. 2018;doi:10.1097/IAE.0000000000001649.
Struthers A, et al. Clin Cardiol. 2008;doi:10.1002/clc.20324.
Tsai DC, et al. Retina. 2014;doi:10.1097/IAE.0000000000000159.
Zhao M, et al. J Clin Invest. 2012;doi:10.1172/JCI61427.