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Central Serous Chorioretinopathy/Choroidopathy

Anna C. S. Tan1,2, Gemmy Cheung2,3,4 and TienYin Wong2,3,41Duke-NUS Medical School, Singapore NationalEye Centre, Singapore, Singapore2Singapore Eye Research Institute, Singapore,Singapore3Duke-NUS Medical School, National Universityof Singapore, Singapore, Singapore4Singapore National Eye Centre, Singapore,Singapore

Synonyms

Central angiospastic retinopathy; Diffuse retinalpigment epitheliopathy; Idiopathic central serousretinopathy/chorioretinopathy

Definition, Pathogenesis, and Etiology

Central serous chorioretinopathy (CSC) is charac-terized by a serous detachment of the neurosen-sory retina that usually affects the macula and theposterior pole (Fig. 1). On fundus fluoresceinangiogram (FFA), there is a classic “smokestack”or “ink blot” pattern of choroidal leakage in aproportion of patients. CSC commonly affectsyoung men aged between 30 and 50 years ofage. The prevalence of CSC is 9.9 cases per

100,000 in men and 1.7 cases per 100,000 inwomen.

The pathophysiology of CSC is unknown andhas been thought to involve multiple mechanismssuch as stasis and ischemia affecting the choroidalcirculation (Nicholson et al. 2013). It has beenhypothesized that a hyper-dynamic and hyper-permeable choroid causes increased hydrostaticpressure in the choroidal vessels. This leads toboth the formation of pigment epithelial detach-ments (PEDs) (Fig. 2) and the breakdown of theretina pigment epithelium (RPE) barrier causingthe leakage of fluid through the RPE cell tightjunctions into the subretinal space, leading to theclassic serous detachment of neurosensory retinaseen (Fig. 1) (Ryan 2012).

Animal models of CSC have shown damage tothe endothelium of the choriocapillaries and fibrinclots, with leakage of fibrin into Bruch’s mem-brane. Newer studies have also shown increasedserum plasminogen activator inhibitor-1(a fibrinolysis inhibitor) levels in patients withCSC, and this may support an underlying throm-botic mechanism. Another study with aqueoussamples showed lower levels of the platelet-derived growth factor (PDGF) in the eyes withCSC than controls, suggesting that abnormalcoagulation and platelet aggregation may also beinvolved in the pathogenesis of CSC (Nicholsonet al. 2013).

Indocyanine green angiography (ICG) hasshown supporting evidence of choroidal hyper-permeability with increased hyper-fluorescence

# Springer-Verlag Berlin Heidelberg 2014U. Schmidt-Erfurth, T. Kohnen (eds.), Encyclopedia of Ophthalmology,DOI 10.1007/978-3-642-35951-4_1074-1

of the choroidal vessels and areas ofchoriocapillary non-perfusion corresponding tofocal areas of hypo-fluorescence (Fig. 3) (Ryan2012; Nicholson et al. 2013). Optical coherencetomography (OCT) with enhanced depth imaging(EDI) in patients with CSC has shown a thickenedchoroid in both the affected and contralateral eyes(Fig. 4). Fibrin deposition in CSC lesions can alsobe observed clinically and on OCT imaging inhumans (Fig. 2) (Agarwal 2012).

For the majority of case, the primary etiology isunknown. However, some secondary etiologicalagents have been described. Corticosteroids, bothexogenous and endogenous, have been stronglyassociated with the development of CSC. Theelevated levels of these compounds activateadrenergic receptors in the sympathetic nervoussystem and are thought to impair theautoregulation of the choroidal vasculature (Nich-olson et al. 2013). Early reports, which linkedexogenous corticosteroid use to the incidence of

CSC, include systemic steroids used for the treat-ment of autoimmune diseases or immunosuppres-sion after organ transplantation. In addition, theuse of topical, intranasal, intra-articular, intramus-cular corticosteroids has been reported to be riskfactors for CSC. Excessive endogenous steroidsin diseases like Cushing’s syndrome and preg-nancy are also associated with CSC. A previousstudy has reported an association of CSC with thetype A personality trait (Ryan 2012). Some otherstudies have reported an association with psycho-social stressors, in addition to inadequate copingmechanisms and the onset of CSC. Some newerstudies have shown that there are also significantmineralocorticoid receptors in the choroid and thismay be involved in CSC pathogenesis.

CSC is also associated less commonly withother diseases, such as systemic lupuserythematosus, sarcoidosis, Crohn’s disease,paraproteinemia, Goodpasture’s syndrome, andthrombotic thrombocytopenic purpura (Agarwal

Central Serous Chorioretinopathy/Choroidopathy, Fig. 1 Spectral domain OCT image (right) showing a CSCwithan underlying RPE breakdown which corresponds to the area of leakage on FFA (white arrow)

Central Serous Chorioretinopathy/Choroidopathy,Fig. 2 Fundus photo showing white-gray discolorationof the fovea due to fibrin deposition and cloudy subretinalfluid. The corresponding spectral domain OCT image

(right) showing a CSC with an underlying PED (whitearrow) and hyper-reflective material within the subretinalspace due to fibrin deposition (red arrow)

2 Central Serous Chorioretinopathy/Choroidopathy

2012). However it is uncertain whether the diseaseitself or the subsequent treatment with corticoste-roids causes CSC (Liew et al. 2013; Nicholson etal. 2013).

Smaller studies have shown weaker associa-tions of CSC; for example, higher level of basalendogenous catecholamines is thought to explainwhy obstructive sleep apnea (OSA) is associated

Central Serous Chorioretinopathy/Choroidopathy,Fig. 3 ICG images showing areas of hyper-fluorescence(white arrow) consistent with choroidal hyper-

permeability and areas of hypo-fluorescence (red arrow)consistent with areas of choriocapillary non-perfusion

Central Serous Chorioretinopathy/Choroidopathy, Fig. 4 Enhanced depth imaging OCT showing a thickenedchoroid in both the eye affected with CSC (red arrow) and the contralateral unaffected eye (white arrow)

Central Serous Chorioretinopathy/Choroidopathy 3

with CSC. In one report, the treatment of OSAwith continuous positive airway pressure (CPAP)resulted in the rapid resolution of bilateralCSC. An association with Helicobacter pylori(H. pylori) infection and CSC has been reportedin recent studies. Thrombotic disease is a possiblepathogenesis of this association. In one study40 % of CSC patients had H. pylori infectionversus 25 % of controls (p = 0.0036). Apartfrom corticosteroid use, other medications like5-phosphodiesterase inhibitors (e.g., sildenafiland tadalafil) have been associated with CS-C. Some case reports have reported a resolutionof CSC after cessation of these medications; how-ever a larger case-control study failed to confirmsuch an association (Nicholson et al. 2013). Anti-biotics, psychopharmacological medications,alcohol, hypertension, and allergic respiratory dis-ease have all been reported in small studies aspotential risk factors of CSC.

A genetic basis to the pathogenesis of CSC isstill not well established. There are numerousreports of familial CSC, and one study found a52 % rate of CSC-like pathology in families ofchronic CSC patients. Despite the clinical find-ings, only a small percentage reported CSC symp-toms. Previous studies have performed analyseson aqueous samples of CSC eyes for variouscytokines and growth factors. Vascular endothe-lial growth factor (VEGF) levels in the aqueouswere not found to be elevated in CSC; howeverthis was controversial, as secondary choroidalneovascularization (CNV) that can be a compli-cation of CSC responds well to anti-VEGF ther-apy. PDGF levels were reported as lower thancontrols, and this could be a possible mechanismof RPE dysfunction. Other cytokines like IL-6,IL-8, and monocyte chemoattractant protein-1were found at similar levels in both CSC andcontrol groups (Nicholson et al. 2013).

Clinical Presentation

SymptomsThe hallmark characteristics of CSC include blur-ring of vision, a relative central scotoma,metamorphopsia, and a hyperopic shift. In some

patients, where the CSC does not involve thecentral macula area, they can beasymptomatic. Once the detachment reaches thecentral macula, it will cause distortion of the pho-toreceptor arrangement. In areas where there iscrowding of the photoreceptors, the patient willexperience macropsia; in other areas with a reduc-tion in the number of photoreceptors per unit area,micropsia will result. Dyschromatopsia with adecrease in color saturation, contrast sensitivity,and a delay in retinal recovery time after exposureto light are other symptoms associated withCSC. A hyperopic shift occurs as the neurosen-sory retinal is pushed forward.

CSC can nominally be classified as acute andchronic; however the definition of the chronicform is not well defined and can range from 3 to6 months of persistent fluid. Other studies haveclassified CSC based on the pathology at the levelof the RPE. “Classic CSC” has pinpoint leaks atthe RPE with minimal focal RPE changes (Fig. 1),while diffuse retinal pigment epitheliopathy(DRPE) has extensive RPE damage and diffuseleakage (Fig. 5) (Nicholson et al. 2013).

The initial episode of acute CSC tends toresolve without serious long-term sequelae.Recurrence of acute CSC, however, is commonand has been reported in 15–50 % of patients inprevious studies. Thirty-three to 50 % of CSCpatients experience the first recurrence within the

Central Serous Chorioretinopathy/Choroidopathy,Fig. 5 FFA of a patient with chronic CSC showing areasof hypo-fluorescence corresponding to areas of RPE atro-phy (white arrow) and areas of diffuse hyper-fluorescenceconsistent with diffuse leakage from the RPE (red arrow)

4 Central Serous Chorioretinopathy/Choroidopathy

first year of follow-up, while 10 %may have threeor more recurrences up to 15 years after presenta-tion. The initial presentation of this disease isusually unilateral, but bilateral involvement isreported to affect up to 40 % of cases. Recentimaging studies have also documented subclinicalstructural changes in the contralateral eye of CSCpatients (Fig. 4). Risk factors for bilateral involve-ment include chronic CSC and CSC associatedwith corticosteroids use (Ryan 2012; Liew et al.2013).

SignsClinical findings include a well-demarcated roundor oval elevation of the neurosensory retinal, ofteninvolving the macula. The foveal reflex isdecreased or absent, and the affected area oftenappears darker than the surrounding area as seenon slit-lamp biomicroscopy (Fig. 6). An

associated PED may be present within or adjacentto the neurosensory detachment in 5–63 % of allcases. This PED can be solitary or multiple and istypically small (Fig. 2). The areas between thedetached and attached RPE appear as a well-circumscribed halo outlining the base of the lesion(Fig. 7). Yellow deposits on the underside of thedetached retina are thought to arise from previousphagocytosis of photoreceptor outer segmentsafter shedding. A yellowish discoloration of thefoveal region is thought to arise from theincreased visibility of the xanthophyll pigment(Fig. 6) (Agarwal 2012; Ryan 2012). The serousfluid within the detachment is mostly clear how-ever in 10 % of cases can be cloudy. In thesecases, fibrin is deposited in the subretinal spaceforming a gray-white fibrinous lesion (Fig. 2),which can be misdiagnosed as focal retinitis, acotton wool spot, or a subretinal neovascular

Central Serous Chorioretinopathy/Choroidopathy,Fig. 6 A fundus photo of a patient (top right) with CSCinvolving the macula, as demonstrated by a reduced fovealreflex and a slightly darker elevated region of the neuro-sensory detachment. The other contralateral eye (top left) is

unaffected. FAF (bottom right) of the CSC shows blockedhypo-fluorescence at the fovea and a mild hyper-fluorescent border around the neurosensory detachmentmore marked inferiorly

Central Serous Chorioretinopathy/Choroidopathy 5

Central Serous Chorioretinopathy/Choroidopathy,Fig. 7 FFA (left) of a patient with CSR and multipleadjacent PEDs. The superior PED (red arrow) is locatedin the area of leakage causing the neurosensory detachmentinferiorly. Corresponding OCT images showing cross

sections of the PED is shown – red arrow (correspondingto top right OCT images) shows actively leaking PED andthe white arrows (corresponding to the middle right andbottom right OCT images) show non-leaking PEDs

Central Serous Chorioretinopathy/Choroidopathy,Fig. 8 (a) Fundus photo (left) showing an inferior bullousretinal detachment from a multifocal chronic CSC and thecorresponding OCT. (b) RPE atrophy tracts connecting the

macula to the inferior bullous detachment as seen on colorfundus photo (left) and hypoautofluorescent area on FAF(right)

6 Central Serous Chorioretinopathy/Choroidopathy

membrane. Some patients develop a bullousserous retinal detachment as the subretinal fluidsettles inferiorly (Fig. 8a). In chronic CSC cases,RPE atrophy on the retina can be seen connectingthe macula to the inferior bullous detachment(Fig. 8b). The vitreous of a CSC patient is clearwith no inflammatory cells.

Diagnostics (Imaging)

Optical Coherence Tomography (OCT)Recent advances in new high-resolution imagingtechniques have enabled better visualization ofstructures and understanding of the underlyingpathophysiology of CSC. Spectral domain OCT(SDOCT) imaging, including enhanced depthimaging (Fig. 4), has enabled imaging of notonly the retinal but the choroid. High-definitionimages of the central serous detachment, serousPEDs, and the underlying choroid have alloweddetailed studies of these structures that were notpossible using conventional slit biomicroscopy.The choroidal layer in CSC patients has beenfound to be thickened when compared to controlsin both the affected and contralateral eyes (Fig. 4).This suggests a much greater incidence of sub-clinical bilateral involvement than previouslyreported. The underlying cause for the thickenedchoroid is not certain; however this is thought tobe related to choroidal vasculature hyper-permeability as seen in ICG angiography(Fig. 3). Choroidal thickness on OCT is a usefulparameter, which can be used to monitor diseaseprogression and response to treatment. Visual acu-ity has been linked with the thickness of the outernuclear layer (ONL) and the integrity of the innersegment ellipsoid zone (EZ). During chronicCSC, photoreceptor apoptosis and subsequentatrophy in the foveal region cause thinning ofthe ONL and disruption of the EZ layer and mayresult in poorer visual acuity (Fig. 9). In manycases, there is also a corresponding atrophic areaof hypo-autofluorescence (AF) seen onautofluorescence (AF) imaging (Fig. 9).

Punctate precipitates and yellow-white mate-rial have been observed in 65 % of CSC patientsand can be seen as hyper-reflective dots on the

OCT image both within the retina and in thesubretinal space (Figs. 10 and 11). This oftencorrelates with clinical slit-lamp findings and fun-dus photography. The nature of these substancesis still unclear, but possible hypothesis includesshed unphagocytosed photoreceptor outer seg-ments and accumulations of fibrin, lipid, or mac-rophages clearing the subretinal space from debris(Liew et al. 2013; Nicholson et al. 2013). Focalareas of RPE breaches can be imaged on OCT, andthis can correspond with leakage on FFA from thechoroid (Fig. 1) (Nicholson et al. 2013). Theseareas adjacent to the leak on FFA frequently aresites for PED formation. Intraretinal cysts andsubretinal fibrosis seen on OCT are also morecommon in chronic CSC and have a poorer visualprognosis (Liew et al. 2013).

Fundus Fluorescein Angiography (FFA)In acute CSC, two distinct patterns of FFA leakagehave been described: ink blot or smokestack. Theink blot pattern is caused initially by the fluores-cein leaking from the fenestrated choriocapillariesacross Bruch’s membrane staining the fluid in thesub-RPE space. This round spot of hyper-fluorescence enlarges concentrically to fill thearea of the PED. In some patients the dye maybe confined to the sub-RPE space but in otherpatients with the dye will diffuse into thesubretinal space and cause the subretinal exudatesurrounding the PED to be hyper-fluorescent(Fig. 12). The smokestack pattern has only beenreported in 10 % of cases. It is caused by the dyefrom the sub-RPE space leaking through a smallpinpoint breach in the RPE at the inferior marginof the PED then flowing upward into thesubretinal exudate in an umbrellalike ormushroomlike pattern (Fig. 13). It has been pro-posed that this pattern of leakage is due to thedifferential specific gravity of the dye and thesubretinal exudates, causing convectional cur-rents. In the late stages, all the subretinal exudateswill be hyper-fluorescent, except in the fovealregion, where it is blocked by luteal retinal pig-ment (Agarwal 2012; Ryan 2012).

In chronic, extensive CSC with PED and atro-phy, RPE window defects may be observed. Inmultifocal CSC multiple areas of leakage may be

Central Serous Chorioretinopathy/Choroidopathy 7

observed, and FFA can help differentiate CSC fromother inflammatory diseases or secondary choroi-dal neovascularization (Fig. 14; Agarwal 2012).Most often the source of leakage is located in theposterior pole, one disc diameter away from thefovea. During FFA, attention should be focused onthe more superior portion of the subretinal detach-ment as it is commonly the site of the leak due togravity. About 30 % of leakage occurs in the supe-rior nasal quadrant, and 25 % occurs in the papillo-macular bundle (Agarwal 2012).

Indocyanine Green Angiography (ICG)Common findings in CSC include a delay in cho-roidal filling, abnormal dilated choroidal vesselsin the early stage, and choroidal hyper-permeability in the late phase (Fig. 3). The areaof abnormality is often much larger than the areaaffected on FFA and is often observed on thecontralateral eye. Patches of hyper-fluorescencein the later stages are caused by leakage into thedeeper choroidal layers. Hypo-fluorescent areason ICG are likely to represent areas of choroidal

Central Serous Chorioretinopathy/Choroidopathy,Fig. 9 A fundus photo (left) of a patient with resolvedCSC showing areas of RPE atrophy corresponding to theareas of hypo-fluorescence on FAF (right). The

corresponding OCT image shows disruption of the EZline and thinning of ONL (red and white arrow). Granularhypo-fluorescence at the fovea region is consistent with apoor visual acuity of 6/90

8 Central Serous Chorioretinopathy/Choroidopathy

Central Serous Chorioretinopathy/Choroidopathy,Fig. 10 Fundus photo and FAF imaging which showyellow-white material, which is also seen as hyper-

reflective dots on OCTwithin the retina and the subretinalspace (white arrows). Intraretinal cysts and schisis changes(red arrow) that can be seen in chronic CSC

Central Serous Chorioretinopathy/Choroidopathy, Fig. 11 Fundus photo and FAF showing the confluent hypo-autofluorescence pattern in areas of RPE atrophy

Central Serous Chorioretinopathy/Choroidopathy 9

non-perfusion, a possible pathogenic mechanismfor this disease (Fig. 3).

Fundus Autofluorescence Imaging (FAF)Fundus autofluorescence (FAF) that employs theuse of either fundus cameras or confocal systemshas also been used to further characterize CSC.Autofluorescent properties such as lipofuscin canrelease light when stimulated by certain wave-lengths. In acute CSC, hyper-autofluorescencedevelops in the areas of the subretinal fluid dueto unphagocytosed photoreceptor outer segments;however this may sometimes be blocked by themacula pigment. A hyper-autofluorescent borderaround the detachment, which is more markedinferiorly, may disappear on resolution of theCSC (Fig. 6). Other areas of focal hyper-autofluorescence correspond to punctate precipi-tates and yellow-white deposits seen clinicallyand on OCT. In chronic CSC or DRPE, changeson FAF are due to RPE damage as well as areas ofactive serous detachment. Patterns previously

described are granular (Figs. 8b and 9) or conflu-ent hypo- or hyper-autofluorescence (Fig. 11).Descending tracts from the macula and opticnerve caused by the movement of subretinalfluid due to gravity can also be imaged on FAF(Fig. 8b). Correlation of FAF and OCT studiesshow that the areas of hypo-autofluorescence cor-respond to the areas of RPE atrophy and can becorrelated with visual acuity if the central maculais affected. A granular FAF pattern was suggestiveof incomplete RPE loss. Hyper-autofluorescencewas not found to correlate significantly withvisual acuity (Ryan 2012).

Multifocal Electroretinography (mfERG)and MicroperimetryFunctional testing in CSC patients has shownreduction in amplitudes on mfERG with outerretinal dysfunction more marked in the centralretina and inner retinal dysfunction more wide-spread extending into the periphery, and this canbe correlated with visual acuity (Agarwal 2012).

Central Serous Chorioretinopathy/Choroidopathy,Fig. 12 FFA showing an “ink blot” pattern of leakage ofthe CSC. Early phases show the filling of the PED (white

arrow), and then in the later stages, there is leakage into thesubretinal space allowing the neurosensory detachment tobe hyperfluorescent (red arrow)

10 Central Serous Chorioretinopathy/Choroidopathy

Implicit times show correlation with OCT find-ings in the paracentral rings. After subretinal fluidresolution, mfERG amplitudes improve, but donot return to normal. Macula sensitivity as mea-sured by microperimetry correlates with findingson the OCT. Retinal sensitivity decreases withincreased disruption of the EZ zone.Microperimetry has also shown a correlation toboth mfERG implicit times and visual acuity.Similar to mfERG in CSC patients, retinal sensi-tivity does not return to normal despite the com-plete resolution of subretinal fluid and 20/20visual acuity (Ryan 2012).

Adaptive Optics (AO)AO allows the imaging of individual photorecep-tors and was used in patient with previously spon-taneously resolved CSC. There was a significantlylesser cone density in these patients compared to

controls, despite most patients having 20/20vision or better. The cone densities correlatedwith the visual acuity and with an intact EZ lineon OCT (Ryan 2012).

Differential Diagnosis

In the majority of the time, the diagnosis of CSCcan be made through a detailed history, slit-lampmicroscopy, and OCT. However other diseasessuch as a congenital optic disc pit, choroidaltumors (e.g., hemangioma, osteoma, malignanttumors), uveal effusion syndrome, and otherinflammatory diseases of the choroid (e.g., Vogt-Koyanagi-Harada disease, sarcoidosis, posteriorscleritis) can be associated with serous detach-ments. Systemic diseases like malignant hyper-tension, toxemia of pregnancy, and disseminated

Central Serous Chorioretinopathy/Choroidopathy,Fig. 13 FFA showing a “smokestack” pattern leakage ofthe CSC where dye from the sub-RPE space leaks through

a breach in the RPE seen in the early phase, then flowsupward into the subretinal exudate in an umbrellalikepattern in later phases

Central Serous Chorioretinopathy/Choroidopathy 11

intravascular coagulopathy can also be associatedwith a neurosensory detachment. Autoimmune dis-eases like systemic lupus erythematosus andpolyarteritis nodosa can cause serous detachmentfrom the disease itself or the subsequent treatmentwith corticosteroids. Age-related macular degener-ation and polypoidal choroidal vasculopathy cancommonly mimic CSC and must be considered inall elderly patients above 50 years old. Ocularcontusion from trauma as well as traction from anincomplete posterior vitreous detachment can alsoresemble a serous detachment. In patients withchronic inferior retinal detachments, the diagnosisof retinoschisis, uveal effusion, or rhegmatogenousretinal detachment should be considered. Occa-sionally, after scleral buckling procedures, theremay be a couple of residual pockets of exudativeretinal detachment which may appear similarto CSC, (Agarwal 2012; Ryan 2012).

Therapy

Acute CSC is a self-limiting disease that usuallyrequires no treatment. Risk factors like psychoso-cial stressors should beminimized. Patients shouldbe screened for CSC inciting drugs like corticoste-roids, catecholamines, and 5-phosphodiesteraseinhibitors and discontinue any unnecessary medi-cation. The use of traditional herbal remedies andsupplements, which may potentially contain corti-costeroids, should also be discontinued. In cases ofsystemic autoimmune disease requiring immuno-suppression, steroid-sparing agents should be con-sidered as an alternative, and a slow tapering off ofthe steroids should be comanaged with a physician(Agarwal 2012; Ryan 2012; Liew et al. 2013;Nicholson et al. 2013).

In cases with no resolution in 3–4 months,chronic cases, or recurrent cases with progressive

Central Serous Chorioretinopathy/Choroidopathy,Fig. 14 FFA of a chronic recurrent multifocal CSC asso-ciated with steroid use, showing a window defect in areas

of RPE atrophy (white arrow) and a superior area ofleakage (red arrow)

12 Central Serous Chorioretinopathy/Choroidopathy

vision loss or in patients with high visual demandsrequiring rapid recovery, treatment can be consid-ered. The main aims of treatment are to improveboth structural and functional outcomes. Theimprovement of symptoms, visual acuity, andthe size of the neurosensory detachment on OCTare all parameters used in clinical practice toassess recovery and treatment effect. The visualpotential and the degree of swelling should beconsidered when planning treatment. For exam-ple, if there is extensive atrophy in the macula andscarring, there may be limited benefit from treat-ment; on the other hand, treating to removechronic subretinal fluid may prevent further dete-rioration. Throughout the course of treatment,there is a risk of the development of secondaryCNV, and this should be diagnosed and treatedearly to prevent further vision loss. Signs of retinalor subretinal hemorrhages and hard exudates adja-cent to the neurosensory detachment or PED maysuggest CNV.

Laser PhotocoagulationThe best current evidence-based treatment of CSCis laser photocoagulation of extrafoveal areas ofleakage or photodynamic therapy (PDT) for areasnearer the fovea. Laser has been thought to hastenthe resolution of CSC, but does not affect the finalvisual acuity in most patients. FFA is required toidentify focal areas of leakage, and laser burns areapplied accordingly. In general, focal laser is onlyrecommended in cases with an extrafoveal(>375 mm) focal area of leakage on FFA angiog-raphy. Diffuse leakage and focal leakage on FFAnearer the fovea should not be treated, due to therisk of scarring and atrophy. The aim of the laser isto stimulate the RPE to absorb to subretinal fluidand to stop further leakage. The exact mechanismof action is unclear. Randomized controls study-ing focal laser treatment to extramacular leakagesites shows a faster resolution of subretinal fluidbut no improvements in visual acuity when com-pared to controls. There was also no improvementin recurrence rates after focal treatment. Second-ary CNV after focal laser treatment was reportedas a potential complication, and patients receivingfocal laser should receive long-term follow-up.

Photodynamic TherapyPhotodynamic therapy that is directed toward thehyper-permeable choroid vessels has beenshown to be safe and effective in the treatmentof CSC. This treatment can promote the resolu-tion in acute CSC and also prevent recurrences.The proposed mechanism of action is choroidalremodeling and thinning of the treated choroid.In trials using PDT to treat neovascularage-related macular degeneration, PDT wasused to cause vaso-occlusion of the choroidalneovascularization. In contrast for CSC, treat-ment with PDT is required only for remodelingof the choroidal vasculature. Hence, modifica-tions to the PDT dosage and laser energy aim toadequately treat CSC while reducing potentialadverse effects. In a previous randomized con-trolled trial, half-dose PDT in patients with acuteCSC has been shown to reduce the risk of persis-tent subretinal fluid at 1 year compared to con-trols. All patients of the treatment group had avisual acuity that was stable or improved in com-pared to only 78.9 % of the control group. Otherstudies have shown that in some patients, multi-ple sessions of PDT may be required to achievecomplete fluid resolution; however this shouldbe balanced against the risk of chorioretinal atro-phy. In one study, the risk of chorioretinal atro-phy was found to be greater in the PDT-treatedeyes than the eyes treated with focal laser, lead-ing to vision loss in some patients. In addition,secondary CNV, choroidal ischemia, and RPErips were reported as other potential complica-tions. Hence, reduced fluence treatment that canbe achieved by reducing the laser treatment time,lowering the laser power or increasing the inter-val between infusion and laser, and reducing theverteporfin dose may be a safer alternative. It isdebatable whether PDT should be performedunder FFA or ICG guidance. A spot size largeenough to cover the area should be appliedavoiding areas of significant RPE atrophy(Ryan 2012; Nicholson et al. 2013). In somestudies, a significant reduction in the choroidalthickness as seen on enhanced depth OCT is seenin the eyes treated with PDT, but a similar changeis not observed in the eyes treated with focallaser.

Central Serous Chorioretinopathy/Choroidopathy 13

Anti-VEGF TherapyVEGF levels were not found to be elevated in theaqueous or plasma in patients with CSC; howeversmall reports of improvements in both anatomicaland functional parameters in CSC have beenreported after the treatment with anti-VEGFagents. However, anti-VEGF agents did notseem to have better outcomes when compared toPDT. Hence when the two treatments are com-pared, the efficacy and safety of intravitreal injec-tions are questionable.

Other TherapiesOther forms of laser therapy like diode micropulselaser and transpupillary thermotherapy have beentrialed in other smaller studies with a limitedfollow-up duration. Overall these therapies showa benefit in the resolution rate of CSC but variableimprovements in visual acuity and function. How-ever, there is insufficient evidence to support thesafety and efficacy of these treatments.

Elevated serum cortisol levels are related to theunderlying pathogenesis of CSC. Anti-glucocorticoids, which inhibit the cortisol path-way such as ketoconazole, mifepristone, finaste-ride, rifampicin, and anti-adrenergics, have beentrialed in small studies with variable results. Fur-ther studies are needed to confirm a significantbenefit. Beta-blockers that cause an adrenergicblockade have been investigated for CSC buthave not shown to be effective.

Carbonic anhydrase inhibitors (CAIs) have beenused to treat CSC, on the basis that it can increasesubretinal fluid reabsorption and retinal adhesion atthe level of the RPE. Only one study on CAIs hasshown that there was a faster resolution rate of acuteCSC but no difference between visual acuity andrecurrence rates between treatment group and con-trols. Similarly, the treatment of H. pylori with sys-temic antibiotics in H. pylori-positive CSC patientsshowed faster resolution of disease but no visualacuity improvement when compared to controls(Ryan 2012). Hypercoagulability has been proposedas another potential mechanism of CSC, and in onestudy, aspirin was shown to improve the rate ofrecovery, reduce rate of recurrence, and result inslightly better visual acuity when compared to con-trols (Ryan 2012; Nicholson et al. 2013).

One small pilot study with no controls hasreported an improvement in both central macularthickness and visual acuity in cases of chronicCSC after treatment with eplerenone, a mineralo-corticoid receptor antagonist. A few larger ran-domized control trials are underway to determinethe efficacy and safety of this promising medicaltreatment for chronic CSC (Bousquet et al. 2013).

Prognosis

The natural history of this disease is that 90 % ofcases will show spontaneous recovery within afew months without significant vision loss. Asmentioned before despite visual acuity recovery,subtle changes can still be seen clinically, on FAF,OCT, and mfERG. However in about 5 % of CSCpatients, visual acuity will not improve to 20/30 orbetter. Fifty percent of patients recur and this ismore common in the first year. Especially in recur-rent and chronic forms of CSC, where there iswidespread RPE atrophy and scarring, irrevers-ible vision loss with reduction in contrast sensi-tivity and color vision can occur. Poor prognosticfactors for visual acuity include a poor presentingvisual acuity and a prolonged duration of theneurosensory detachment. In a small group ofpatients (up to 6 %), a secondary CNV candevelop and cause visual loss. Spontaneous reso-lution of a small PED is more common than inlarger lesions; however the visual acuity usuallyremains preserved despite a large PED. Despitecomplete resolution of a serous detachment, resid-ual pigmentary changes and mottling can still beobserved. High-resolution imaging shows sub-clinical structural changes occur despite regaining20/20 vision; hence CSC should not be considereda benign disease (Agarwal 2012; Ryan 2012).

Epidemiology

The incidence rates of CSC in the largestpopulation-based study in Minnesota, USA,were estimated as 9.9 cases per 100,000 in menand 1.7 cases per 100,000 in women. CSC isthought to have a higher incidence in Asian

14 Central Serous Chorioretinopathy/Choroidopathy

populations followed by Caucasian populationsand affects African-Americans the least (Ryan2012; Liew et al. 2013). In one study with ChineseSingaporeans, the rates of multifocal and bilateralinvolvement of CSC were higher than in a similarwhite population. Another study reported thatdespite lower rates in African-Americans, thesepatients have worse visual acuity throughout thecourse of disease suggesting a greater severity ofthe disease (Liew et al. 2013).

CSC is more common in males than in femaleswith previous ratio reported as 6:1. The age ofonset ranges between 30 and 50 years of age.Older CSC patients tended to have a higher rateof chronic CSC with diffuse RPE loss and some-times the development of secondary choroidalneovascularization (CNV) (Ryan 2012).

References

Agarwal A (2012) Gass’ atlas of macular diseases,vol 1, 5th edn. Elsevier Saunders, Amsterdam,pp 66–69

Bousquet E et al (2013) Mineralocorticoid receptor antag-onism in the treatment of chronic central serouschorioretinopathy: a pilot study. Retina33(10):2096–2102

Liew G et al (2013) Central serous chorioretinopathy: areview of epidemiology and pathophysiology. ClinExperiment Ophthalmol 41(2):201–214

Nicholson B et al (2013) Central serous chorioretinopathy:update on pathophysiology and treatment. SurvOphthalmol 58(2):103–126

Ryan SJ (2012) Retina, 5 edn, vol 2. Elsevier HealthSciences, Netherlands, pp 1291–1305

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