Chapter 127 – Central Serous Chorioretinopathy
WILLIAM J. WIROSTKO
JOSE S. PULIDO
• An idiopathic chorioretinal disorder characterized by serous detachment of the neural retina in the macular region.
• One or more focal areas of subretinal fluid in the macula.
• One or more focal leaks at the level of the retinal pigment epithelium.
• Retinal pigment epithelial detachment.
• Mottling of the retinal pigment epithelium.
• Yellowish white subretinal deposits.
• Unilateral or bilateral involvement.
• Dependent, bullous retinal detachment.
Central serous chorioretinopathy (CSC) is a common retinal disorder characterized by an idiopathic serous neural retinal detachment in the macular region ( Fig. 127-1 ). Since its initial description as relapsing central syphilitic retinitis by von Graefe in 1866, it has been referred to by many names, including central serous retinopathy, central serous pigment epitheliopathy, and central serous retinitis. The most common symptoms of CSC include metamorphopsia, blurred vision, and micropsia. Visual disturbances typically take several months to resolve. The most surprising aspect of the disease is the relative preservation of retinal function despite prolonged separation from the retinal pigment epithelium (RPE). Occasionally, the macular detachment may fail to resolve spontaneously; for these eyes, laser photocoagulation appears to be beneficial, as it accelerates the resorption of subretinal fluid and improves vision.   
EPIDEMIOLOGY AND PATHOGENESIS-11
Typically, CSC affects men aged 20 to 50 years. No case has been reported in a person younger than 20 years. In patients older than 50 years, CSC does occur, but it can be difficult to distinguish from age-related macular degeneration. An increased frequency may exist in intelligent individuals engaged in visually demanding work who display type A personality traits or who are experiencing physical strain or emotional stress. A history of migraine-type headaches may be elicited. Also, CSC has been associated with vasoconstrictive agents, endogenous hypercortisolism, smoking, and the systemic use of corticosteroids (oral, intranasal, and inhaled),  psychopharmacological agents, alcohol, antibiotics (oral), and antihistamines (oral). It can be produced in animals by repeated intravenous epinephrine (adrenaline) injections. 
Figure 127-1 Fundus photograph of central serous chorioretinopathy. Note the neural retinal detachment the size of two disc diameters in the macular region, the pigment epithelial abnormalities inferonasal to the fovea, and the numerous tiny yellow dots on the undersurface of the retina. (Courtesy of T.C. Burton, MD.)
Figure 127-2 Fluorescein angiogram of central serous chorioretinopathy. A, Early phase reveals focal leakage nasal to the macula. B, Late phase demonstrates pooling of the dye within the subneural retinal space.
The understanding of the pathogenic accumulation of subneural retinal fluid in the macular region is limited. Few pathological studies have been performed, and the observations from angiographic, clinical, and experimental models are subject to interpretation. It is well known, however, that the subneural retinal fluid originates from the choroid. The leakage of dye through an abnormal focal defect at the level of the RPE and its
Figure 127-3 Indocyanine green angiogram of central serous chorioretinopathy. Contrast enhancement reveals a focal area of hyperfluorescence during the midphase of the study. Fluorescein angiography demonstrated no leakage in the corresponding area.
accumulation in the subneural retinal space are seen clearly on fluorescein angiography  ( Fig. 127-2 ).
The cause of the focal RPE leak is unclear. At first it was believed that a simple breakdown of the blood-retinal barrier at the RPE level was responsible for the leak. However, this theory does not explain the beneficial effect of the permanent RPE barrier breakdown produced during laser photocoagulation. Later, it was suggested that the subneural retinal fluid pooled secondary to a collection of pathologically hypersecreting RPE cells, but this theory fails to explain the widespread choroidal hyperpermeability seen with indocyanine green angiography ( Fig. 127-3 ).
Increasing evidence implicates an abnormal choroidal circulation as the cause of CSC. Using indocyanine green angiography, Prunte and Flammer showed delayed choroidal capillary lobular filling in areas of hyperpermeability. They proposed that localized capillary and venous congestion in the affected lobules impaired the circulation, produced ischemia, and allowed increased choroidal exudation and a focally hyperpermeable choroid. This allows excess choroidal fluid to accumulate and produces a retinal pigment epithelial detachment (RPED). As the detachment grows, the target junctions between RPE cells are broken, and a focal defect of the blood-retinal barrier develops. Choroidal fluid passes through this opening and produces a neural retinal detachment. Interestingly, recent studies reveal that corticosteroids can influence the production of nitric oxide, prostaglandins, and free radicals within the choroidal circulation. All three participate in the autoregulation of blood flow within the choroid.
Although unilateral metamorphopsia is the classic symptom of CSC, patients also may present with unilateral blurred vision, micropsia, impaired dark adaptation, color desaturation, delayed retinal recovery time to bright light, and relative scotoma. Visual acuity ranges from 20/15 (6/5) to 20/200 (6/60) but averages 20/30 (6/9). The visual acuity may improve with hyperopic correction. Symptoms typically resolve after several months but may linger even after the fluid resolves; only rarely do they persist indefinitely. Permanent sequelae include metamorphopsia, decreased brightness perception, and altered color vision.
Also, CSC can present as a bullous, inferior nonrhegmatogenous peripheral retinal detachment. The presence of RPE atrophic tracts from the macular region to the peripheral detachment, seen best with fluorescein angiography, reveals the true diagnosis and source of the subretinal fluid.
A chronic form of CSC exists as well. It occurs in about 5% of cases, most commonly in older individuals and in patients receiving corticosteroids.   The use of psychopharmacological agents may also predict its development. Chronic CSC is characterized by a diffuse retinal pigment epitheliopathy that progresses in conjunction with persistent or intermittent subretinal fluid. The retinal detachments tend to be shallow and more diffuse than in the classic form. The visual prognosis is more guarded.
The diagnosis of CSC is clinical, with confirmation by fluorescein angiography. Although in most cases the diagnosis can be made confidently without ancillary testing, the information derived from angiography is critical to detect the extent of the retinal abnormalities and to exclude the presence of other pathology.
Biomicroscopically, a transparent blister in the posterior pole between the neural retina and the RPE is observed. This is best seen through a fundus contact lens with a wide light beam, set slightly off axis. Signs that suggest the presence of a retina-RPE separation include beam splitting as the light traverses the serous space, an increased distance between the retinal vessels and their shadows, and an absent foveal reflex. Shallow detachments may be difficult to demonstrate clinically.
The subretinal serous fluid within the blister often is transparent. This fluid may have protein and fibrin and be turbid or yellowish, especially in patients who are pregnant or have increased pigmentation, concurrent diabetes, or RPED.  It is believed that the small dotlike deposits that form on the posterior surface of the retina or on the anterior surface of the RPE cells under the area of the detachment represent precipitates of this protein. This is noted best when the fluid component is resolving. Diffuse deposits of serous proteins can produce a whitish retinal appearance that mimics intraretinal edema. A normal retinal thickness and transparency help distinguish this from true retinal edema.
Oval yellow-gray elevations beneath the detachment also may be seen. These are generally less than one fourth of a disc diameter in size and are surrounded by a faint grayish halo. Fluorescein angiography identifies them as RPEDs and frequently demonstrates the focal RPE leaks responsible for the neural retinal detachment within their borders. Because subretinal exudative fluid may track inferiorly in response to gravity, a leaking RPED may lie beyond the superior margin of its retinal detachment. Numerous factors can help differentiate an elevated RPED from a shallow focal retinal detachment:
• An RPED obscures the choroidal pattern (this characteristic may abate as the RPE cells in the RPED atrophy).
• The boundary of the RPED typically is better defined than the edge of the retinal detachment.
• The light beam reflex is bowed forward toward the observer, preventing visualization of the sub-RPE space.
A large RPED must also be differentiated from an amelanotic melanoma or metastatic lesion to the choroid. Both can appear dome-shaped, solid, and nontranslucent and produce an overlying neurosensory detachment.
The presence of cystic retinal degeneration, fine RPE mottling, or RPE clumping suggests chronicity of the present episode or a history of a previous CSC episode ( Fig. 127-4 ). Additional ophthalmoscopic findings, such as lipid or hemorrhage, are rare and should call into question the diagnosis of idiopathic CSC. The fellow eye may show evidence of either concurrent or previously resolved CSC, manifested as focal areas of RPE rarefaction or small asymptomatic RPEDs.
Fluorescein angiography plays an important role in the evaluation of CSC. It is used to exclude the presence of other pathologies that produce neural retinal detachments and to confirm the diagnosis. Classically, dye from the choroid leaks through a focal RPE defect and pools in the subretinal space. In
Figure 127-4 Fundus photograph of an eye with resolved central serous chorioretinopathy showing chronic pigmentary changes. (Courtesy of W.F. Mieler, MD.)
more than 75% of patients, this pooling occurs within 1 disc diameter of the fovea. Less pooling may be observed in older lesions in which the RPE exudate has become inspissated.  When fluorescein angiography is atypical, indocyanine green angiography can help exclude the presence of other pathology. Indocyanine green angiography of CSC classically reveals bilateral multifocal hyperfluorescence in affected and unaffected areas of the choroid. These appear during the midphase of the angiogram and are later silhouetted against larger choroidal vessels as the dye diffuses through the choroid.
Optical coherence tomography is a new, noninvasive technique that can demonstrate the presence of subretinal fluid. In cases of CSC, optical coherence tomography has been used successfully to quantify the amount and extent of subretinal fluid and to demonstrate thickening of the neurosensory retina.
Serous elevations of the neurosensory retina in the macular region can be produced by numerous diseases of the choroid, RPE, and retina. These include choroidal neovascularization, optic disc pits, polypoidal choroidal vasculopathy, choroidal melanoma, choroidal metastasis, and peripheral retinal breaks. Choroidal hemangioma, uveitis, Harada’s disease, optic neuritis, papilledema, vitreous traction, macular holes, and systemic hypertension can produce neural retinal detachments as well.
In particular, CSC must be differentiated from a neural retinal detachment secondary to subretinal choroidal neovascularization, polypoidal choroidal vasculopathy, or an optic disc pit. These three diseases mimic CSC by producing similar clinical findings, including neural retinal detachment, RPE changes, RPED, and subretinal exudate, but they have a significantly different pathophysiology, prognosis, and treatment. Consequently, their presence should be excluded with fluorescein angiography in all cases of presumed CSC. If fluorescein angiography is inconclusive, one can perform indocyanine green angiography. Indocyanine green angiography of subretinal choroidal neovascularization usually reveals only one area of hyperfluorescence that progressively enlarges during the later frames of the study. Indocyanine green angiography of polypoidal choroidal vasculopathy demonstrates small-caliber, polypoidal choroidal vascular lesions and no areas of choroidal hyperpermeability. If the possibility of a choroidal neovascular membrane remains despite angiography, it may be prudent to observe the patient and repeat angiography 2 weeks later. An area of CSC leakage should remain constant or regress with time, whereas a choroidal neovascular membrane will likely grow.
Usually, CSC is an isolated idiopathic ocular disorder. Patients may, however, exhibit various CSC risk factors, including type A personality traits or a recent episode of stress.
Also, CSC has been associated with hypercortisolism and systemic corticosteroid use.  The observation of increased CSC symptoms during periods of increased steroid use, and their subsequent resolution when dosages are decreased, led to this discovery. Bouzas et al. reported a CSC prevalence of 5% among patients with endogenous Cushing’s syndrome.
Multiple diseases that share the underlying choroidal vascular dysfunction have been linked to classic CSC or to a visual syndrome that mirrors the disease. These include accelerated hypertension, pregnancy, dialysis, organ transplantation, and systemic lupus erythematosus.     
The benign course of CSC and the low incidence among the elderly have limited the number of pathological studies. In those few performed, the RPE, choroid, and retinal vessels appear normal. The only histopathological changes observed include serous RPEDs, serous detachments of the cuticular portion of Bruch’s membrane, and cystic degeneration in the outer layers of the detached neural retina. 
The treatment of CSC is laser photocoagulation to the site of fluorescein leakage. Although this has been proved to reduce the duration of the serous detachment, it has no effect on the final visual prognosis and consequently is reserved for select patients.  It is the only therapy proved beneficial by large clinical trials.
The technique of laser photocoagulation involves using a green-wavelength laser to produce a light scar over the focal RPE leak. Typically, 6–12 laser burns of 50–200?µm spot size at 0.1-second duration and 75–200?mW are used. Permanent RPE change is induced at the site of the laser scar. It has been suggested that while the scar facilitates the absorption of subretinal fluid via the choroid, it also destroys an area of abnormally hypersecreting RPE cells. The absence of any beneficial effect when the laser scar does not overlie the focal choroidal leak suggests the presence of a focal RPE abnormality.
The only definite benefit from laser therapy is its ability to decrease the duration of the neurosensory detachment. This has been documented in numerous studies.  In 1974, Watzke et al. demonstrated that the median duration of disease decreased from 23 weeks in untreated eyes to 5 weeks in treated eyes. Whether laser therapy is of benefit in decreasing the risk of recurrence remains an unresolved question. The 0% rate of recurrence obtained by Yap and Robertson disagrees with the 34% recurrence rate obtained by Watzke et al. Both figures compare favorably with the 45% recurrence rate found by Klein et al. for untreated eyes.
Complications from laser photocoagulation include choroidal neovascularization and central scotoma. Although rare, they can be visually devastating ( Fig. 127-5 ). Complications may be reduced by using larger spots sizes, employing lower intensities, and avoiding the capillary-free zone. The rapid development of a choroidal neovascular membrane following laser photocoagulation suggests the possibility of an initial misdiagnosis. Subfoveal choroidal neovascularization associated with CSC may be treated with submacular surgery.
Because most CSC episodes resolve spontaneously, laser treatment is reserved for patients who fail to improve after 4–6 months, demonstrate permanent changes from CSC in the other eye, demonstrate multiple recurrences, or require improved vision for work. Treatment should be avoided if the leak occurs within 200?µm of the center of the foveal avascular zone. Eyes with chronic CSC unresponsive to laser treatment may benefit from photodynamic therapy.
Figure 127-5 Choroidal neovascular membrane after laser photocoagulation for central serous chorioretinopathy. A, Fundus of an eye with a 2-year history of recurrent CSC. Note the neurosensory detachment and the numerous fine yellow deposits under the retina. B, Fundus showing subretinal blood at the treatment site. C, Late-frame fluorescein angiogram demonstrating dye leakage from a choroidal neovascular membrane. (Courtesy of W.F. Mieler, MD.)
Despite isolated reports, no medical therapy is of proven value. Ongoing studies are still investigating the beneficial role of systemic ß-blockers.  The association of corticosteroids with CSC suggests that dosages should be reduced if a patient is receiving exogenous supplementation.
COURSE AND OUTCOME
Generally, the visual prognosis is good. The majority of patients suffer no significant permanent visual loss. In a series of 34 eyes with CSC followed for an average of 23 months without treatment, visual acuity was no worse than 20/40 in any eye. This was despite large neural retinal detachments, multiple RPE leaks, cystoid macular changes, persistent RPEDs, and marked visual loss during acute episodes. The persistent Amsler’s chart changes present in 24 of 27 eyes were described as visually insignificant and causing no difficulty. Although visual acuity usually improves, patients may continue to have persistent metamorphopsia. After resolution of an episode of CSC, multifocal electroretinogram may be helpful for suggesting the risk of recurrence.
Rarely, CSC can produce significant visual damage, usually caused by the chronic form of the disease. RPE atrophy, a metallic sheen at the level of the RPE, drusen, and choroidal neovascularization have also been described in eyes with untreated CSC. Cases called “CSC” exist in which bullous neurosensory detachments extend from the posterior pole to the most dependent part of the retina.
Follow-up fluorescein angiography of eyes with CSC suggests that, in certain patients, CSC may herald a bilateral progressive RPE disturbance known as chronic CSC. It remains unresolved whether a history of CSC exacerbates the natural course of age-related macular degeneration. However, recent studies suggest that CSC in older individuals is more frequently associated with the formation of choroidal neovascularization than in younger patients.
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