Central Serous Chorioretinopathy and Glucocorticoids

Abstract

Central serous chorioretinopathy is a relatively common retinal disease characterized by the accumulation of subretinal fluid at the posterior pole of the fundus, creating a circumscribed area of serous retinal detachment. It typically affects young and middle-aged men with no previous medical and family history, and no systemic symptoms or signs. However, it has been noted that central serous chorioretinopathy is associated with different conditions, characterized by exposure to increased levels of endogenous or exogenous glucocorticoids. In fact, central serous chorioretinopathy has been described in patients with endogenous Cushing's syndrome. It is also prevalent in patients with type-A behavior, and following stressful events, and pregnancy probably represents a risk factor for central serous chorioretinopathy; these conditions are characterized by endogenous hypercortisolism. In addition, many cases of central serous chorioretinopathy have been described during or following treatment with glucocorticoids, administrated by any route, for various systemic or ocular conditions. Central serous chorioretinopathy, when related to the exposure to exogenous glucocorticoids, has a less prominent male predilection, presents more often with a chronic or atypical form, and is frequently bilateral. Furthermore, treatment of central serous chorioretinopathy with glucocorticoids was found to exacerbate the clinical picture. Based on these observations it could be suggested that glucocorticoids may be involved in the development of central serous chorioretinopathy, even though the exact pathogenic mechanism remains unclear. Glucocorticoids should not be used in the treatment of central serous chorioretinopathy and central serous chorioretinopathy should be added to the list of ocular complications of glucocorticoids.

Introduction

Central serous chorioretinopathy is characterized by the accumulation of subretinal fluid at the posterior pole of the fundus, causing a circumscribed area of retinal detachment. When the detachment spreads into the central macular area, the patient typically develops metamorphopsia, a positive scotoma, and micropsia. Visual acuity is often only moderately decreased and may be improved with the addition of a small hyperopic correction. If the detachment does not extend to the central macular area, the patient is usually asymptomatic. The diagnosis is based on the ophthalmoscopic findings and results of fluorescein angiography.⁷⁷ In most cases CSCR resolves within a few months and visual acuity returns to 20/25 or better, but small, funduscopically visible, pigment epithelial alterations usually remain; complaints of metamorphopsia, micropsia, color vision changes, and/or darkening of the central visual field often remain as well.64, 77, 125 Thirty to fifty percent of patients have one or more recurrences.24, 32, 62, 82

Central serous chorioretinopathy typically affects young and middle-aged adults, with men affected more commonly than women.18, 77 The patients' medical history, family history, and general physical findings are in most cases unremarkable.⁷⁷ The pathogenesis of CSCR remains unclear.37, 77

Medical treatments have no proven influence on the disease.75, 77, 137, 154 Laser photocoagulation has been widely used.24, 26, 32, 49, 62, 82, 178, 193, 202 However, the results of different studies on this subject are controversial and not conclusive, and laser photocoagulation remains recommended only in selected cases.37, 77

Endogenous glucocorticoids are secreted by the cortex of the adrenal glands. In humans, cortisol is the principal glucocorticoid. Adrenocorticotropic hormone (ACTH), which is secreted by the pituitary gland, is the primary regulator of adrenal cortisol secretion and the hypothalamic hormone, corticotropin-releasing hormone (CRH), is the main stimulator of ACTH production. Cortisol regulates the activity of the hypothalamic-pituitary-adrenal axis (HPA axis) by negative feedback on both ACTH and CRH. Numerous factors such as metabolic, physical, and emotional stress increase glucocorticoid secretion by increasing the hypothalamic secretion of CRH.85, 100 Furthermore, chronic, excessive production of endogenous glucocorticoids leads to the development of endogenous Cushing's syndrome. This may result from excessive ACTH secretion by pituitary corticotropinomas or ectopic ACTH-secreting tumors, or from the autonomous secretion of cortisol by benign or malignant adrenal tumors or dysplastic adrenals.¹⁶¹

In addition to endogenous Cushing's syndrome, patients may be exposed to increased levels of glucocorticoids after exogenous administration. In fact, as a consequence of their anti-inflammatory properties glucocorticoids are widely used in the treatment of inflammatory and allergic disorders. A large spectrum of synthetic glucocorticoids with different structures and properties are used in pharmacology.¹⁴⁸ An extensive list of systemic and ocular complications of this treatment has been reported.8, 28, 31, 65, 85, 148, 184, 209

Despite the lack of proof for their efficacy, glucocorticoids were widely used for many years as a treatment for central serous chorioretinopathy.102, 147, 173 However, as early as in 1966, Jain and Singh reported the occurrence of maculopathy which resembled central serous chorioretinopathy in a patient receiving glucocorticoid therapy for Reiter's syndrome.¹¹⁰ In 1973, Wessing noted that “there are some cases which show an increase of the subretinal transudate under systemic steroid treatment, and we may observe the development of CSCR during systemic cortisone treatment for other reasons”²²⁰ while in 1977, Gass also reported that glucocorticoids, used for the treatment of CSCR, seem to intensify the condition.⁷⁸

Nevertheless, the association between glucocorticoid treatment and the development or exacerbation of CSCR failed to attract attention until several Japanese authors, including Wakakura and Harada, clearly indicated the possibility of such a relationship. In fact, Wakakura et al and Harada et al presented several cases and reviewed an impressive number of case reports which had appeared in the Japanese literature describing CSCR occurrence during glucocorticoid treatment.91, 214, 215, 216

In 1993, Bouzas et al reported the development of CSCR in patients with endogenous Cushing's syndrome.²³ They also stressed the fact that other conditions associated with an increased incidence of CSCR, such as pregnancy, stress, and type-A personality, are characterized by endogenous hypercortisolism and concluded that glucocorticoids may play a role in the development of CSCR. Subsequently, during the past few years, many articles have appeared in the literature providing additional arguments to strengthen this hypothesis.

In this review, we will try to summarize the bibliographic evidence related to the possible association between CSCR and glucocorticoids.