Clinical, experimental, and genetic studies on the etiology of central serous chorioretinopathy

Central serous chorioretinopathy (CSC) is a specific and relatively common
early-onset form of macular degeneration, that often occurs in patients in the
professional active age range. This eye disease can present as an acute or a
chronic disease.
CSC is a specific form of macular degeneration, in which there is an
accumulation of fluid under the retina, which causes a detachment of the
neuroretina.This fluid accumulation under the retina appears to be caused by a
dysfunction of the retinal pigment epithelium (RPE) as a result of
hyperpermeability and swelling of the underlying vascular layer of the eye, the
choroid. A prolonged neuroretinal detachment in the macula leads to permanent
central visual loss due to photoreceptor atrophy. Such a loss of visual acuity,
with image distortion, loss of colour and contrast vision may have a high
impact on a patient*s personal and professional life. Early diagnosis and
treatment is desirable to try to improve the visual outcome and quality of
life. After all, long-term follow-up studies have shown that the natural course
of chronic CSC often results in permanent visual loss.
An association between severe psychosocial stressful events and CSC has been
found, especially in patients with poor coping mechanisms. Both endogenous and
exogenous Cushing*s syndrome are associated with CSC. Although little is known
about the causes of CSC, circumstantial evidence suggests that the immune
system may participate in the etiology of CSC, since CSC can occur in various
immune-mediated diseases such as membranoproliferative glomerulonephritis and
systemic lupus erythematosus. In age-related macular degeneration, a disease
that shows overlapping features with CSC, complement activation has also been
found to play an important role. Several studies have found increased serum
complement activation in age-related macular degeneration. With the study we
hope to learn more about the etiology of CSC.

The key objectives of this study are to identify both the genetic background
and pathophysiological mechanisms that underlie CSC. To achieve this we will:
1) Perform genetic analysis and ophthalmological examination in a cohort of
sporadic CSC patients and a database of families with CSC to assess the role of
genetic factors and possible genotype-phenotype correlations in CSC.
2) Assess whether there is evidence of serum complement activation in CSC.
3) Analyse possible abnormalities in endocrinological factors in CSC, such as
cortisol and testosterone levels and sensitivity to these hormones in CSC
patients.
4) Perform ophthalmological examination of the retinal phenotype and choroidal
thickness in individuals at risk of developing CSC, including patients with
Cushing*s syndrome, Conn*s syndrome, patients who receive solumedrol (a
corticosteroid) during acute rejection of a renal transplant, and post kidney
transplantation patients receiving corticosteroids.

1) Genetic analysis and ophthalmological examination in a cohort of sporadic
CSC patients, in known families with CSC, and in a healthy control group.
* Genetic case-control study.

2) Analysis of serum and plasma complement activity in CSC patients and in a
healthy control group.
* Analysis of serum and plasma complement factors.

3) Cross-sectional endocrinological analysis of cortisol and testosterone
exposure- and sensitivity in CSC patients and in controls.
* Both cross-sectional (treated CSC patients in remission) and prospective (de
novo patients with active CSC) evaluation of cortisol and testosterone
exposure- and sensitivity. These results will be compared to a control group of
patients, matched for blood pressure and diabetes/glycosylated haemoglobin.

4) Detailed evaluation of the retinal phenotype and choroidal thickness in
patients with documented endogenous corticosteroid excess (Cushing*s syndrome),
primary hyperaldosteronism (Conn*s syndrome) or exogenous corticosteroid excess
(post kidney transplantation patients who receive corticosteroids) will be
performed. These results will be compared to a control group of patients,
matched for blood pressure and diabetes/glycosylated haemoglobin, without
corticosteroid overexposure. Also assessment of intrinsic differences in
glucocorticoid sensitivity between patients will be performed, using blood
samples.
* Both cross-sectional and prospective

The only invasive procedure, which will be performed in some of the patients
participating within this study, is a venepuncture. This procedure has a
minimal risk on the development of pain, a subcutaneous edema, of a phlebitis.
The other procedures, which will be performed within this study, are part of
standard clinical care.