Central serous chorioretinopathy

Definition

Active CSC is characterized by detachment of the neurosensory retina caused by accumulation of serous fluid between the photoreceptor outer segments and the RPE in combination with monofocal or multifocal changes in the RPE. The detachment should not be attributable to holes or tears in the retina, neovascularization, inflammation, neoplasia or specific hereditary disease. The retinal detachment usually involves the fovea but exceptions to this rule can be found. Unlike hereditary chorioretinal degenerations, the pattern of RPE anomaly in CSC is geometrically irregular in that it generally lacks symmetry about the facial midline (as seen in retinitis pigmentosa) and rotational symmetry about the centre of the fovea (as seen in bull's eye dystrophies). The diagnosis of chronic CSC requires multifocal or diffuse RPE depigmentation combined with a serous detachment of the retina. Inactive CSC, defined by the retina being fully attached, may be diagnostically challenging because the residual abnormalities of the RPE may resemble those of other conditions, but often a history characteristic of acute CSC dating back years or decades can be elicited. Neovascular CSC is usually a sequel of chronic CSC. Macular haemorrhage in CSC should always lead to the suspicion of subretinal neovascularization (Schatz et al. 1977).

Past medical history

Patients are generally in good health. Some may have experienced previous episodes of transient blurred vision.

Family history

Reports of two or more cases within a family suggest that a hereditary predisposition to CSC may exist (Oosterhuis 1996; Park et al. 1998). A fluorescein angiography study of siblings, uncles and nieces of 27 patients with chronic CSC demonstrated RPE atrophy in 35 of 80 relatives, of which 22 were classified as unrecognized cases of chronic CSC (Weenink et al. 2001). The available studies are not informative as to the mode of inheritance.

Symptoms

CSC of recent onset is associated with blurred vision with a relative central scotoma, metamorphopsia, dyschromatopsia, micropsia, hypermetropization and reduced contrast sensitivity. In some patients, CSC is preceded or accompanied by migraine (Gass 1967).

Symptoms are usually confined to the centre of the visual field and frequently the primary complaint is one of transiently seeing a dark spot in the centre of the visual field in one eye (Fig. 1), with or without accompanying metamorphopsia (Fig. 2). Best-corrected visual acuity ranges from 20/20 to 20/200; a hyperopic shift is a common finding, corresponding to the anterograde displacement of the neurosensory fovea (Klien 1956; Peyman & Bok 1972). Scanning laser ophthalmoscopic microperimetry has demonstrated a 10–100 fold reduction of sensitivity within the affected part of the visual field (Toonen et al. 1995). The dark spot, which is the subjective representation of a relative scotoma in the centre of the visual field (Faschinger & Brunner 1982), is usually most prominent in the morning immediately after awakening. Patients often report seeing it most clearly when opening their eyes and looking at the ceiling of their bedroom, presumably because the typical ceiling is bright white and unstructured. The spot can often be made visible later in the day by blinking. These characteristics are typical of a relative scotoma, and like the relative scotoma produced by light (i.e. an after-image) it fades within a few seconds, presumably because of the Troxler effect, a retinal function that subtracts any stationary background stimulus (Fig. 3). The entopic spot produced by a serous retinal detachment can be made visible to the patient by using the pinhole flicker test, as when the retinal vessels are visualized (Iwami 1995). The patient looks at a brightly lit uniform surface through a pinhole held 0.5–1.0 cm in front of the eye. The pinhole plate is then moved sideways a few millimetres back and forth at a frequency of about 4 Hz. In contrast to acute CSC, patients with sequels of CSC or chronic CSC may have blurred vision, but rarely (if ever) complain of seeing a dark spot.

Visual function and psychophysical tests

Functional testing of eyes with serous retinal detachment has demonstrated that a minimal relative afferent pupillary defect may be present, as may reduced critical flicker-fusion thresholds, prolonged visual evoked potential (VEP) latencies, dyschromatopsia – most often with a tritan axis (Williams 1976) – and depression of central visual field sensitivity. After resolution, the afferent pupillary defect and critical flicker-fusion thresholds are first to improve, followed by visual acuity, VEP latency and colour discrimination. The threshold differential light sensitivity in the central visual field is slowest to improve (Folk et al. 1984).

Biomicroscopy

The subretinal fluid in CSC is commonly clear, but granular or fibrinous deposits may be present in the subretinal space (Ie et al. 1993; Wang et al. 2002). The accumulation of granular material between the RPE and the neurosensory retina increases in relation to the duration of symptoms (Wang et al. 2005). Other characteristics include the absence of the normal foveal light reflex and a distinct visibility of the yellow foveal xanthophyll, presumably caused by increased scatter in the thickened perifoveal tissue of the detached retina (Spaide et al. 1996; Gass 1991; Ie et al. 1993).

Despite a marked propensity of the serous detachment to involve the fovea, to be centred in the fovea and to reach its maximum height in the fovea, the primary lesion in the RPE is rarely subfoveal. Indeed, it can be located anywhere in the posterior pole within or immediately outside the temporal vascular arcades (Gomez-Ulla et al. 1993). Large bullous detachments often show the phenomenon of subretinal fluid shifting position with changes in posture.

Abnormalities of the RPE are present, by definition, in CSC. When most prominent, these abnormalities are seen as one or more yellow spots or a small pigment epithelial detachment. The RPE detachment can occasionally be seen to be ruptured, the rupture being the site of profuse angiographic leakage (Fig. 5). Recent optical coherence tomography (OCT) studies suggest that retinal pigment epithelial detachment may be present in most cases of CSC (Saito et al. 2005; van Velthoven et al. 2005; Mitarai et al. 2006). It is unknown whether small sources of leakage are indeed small pigment epithelial detachment beyond the resolution of current imaging techniques. Less prominent abnormalities at the level of the RPE can be made visible during biomicroscopy using choroidal retroillumination. These appear as minute refractile granules deep in the retina. Unlike degenerative conditions such as retinitis pigmentosa or photocoagulation scarring, geographic RPE atrophy does not occur in CSC, whereas hypopigmented RPE is a frequent finding, characterized biomicroscopically by translucency without transparency. It is not often that true hyperpigmentation occurs, but dense subretinal deposits can look like hyperpigmentation when seen in choroidal retroillumination. Hypopigmentation of the RPE is more prominent on fluorescein angiography than on biomicroscopy. The diagnosis of CSC is supported by CSC-compatible RPE changes in the fellow eye.

Less frequent manifestations of CSC include retinal capillary dilation, choriocapillaris atrophy, atrophic tracts of the RPE and inferior peripheral dependent serous retinal detachment (Yannuzzi et al. 1984). When telangiectasia, leakage, retinal lipid deposition and/or cystoid macular oedema are seen (Yannuzzi et al. 1984), these features likely attest to the presence of choroidal neovascularization (CNV).

The subretinal fluid in CSC is usually clear, but the subretinal cavity may contain granular or cloudy material of a pale yellowish hue (Spaide et al. 1996). Non-granular subretinal material is often called fibrin. The subretinal material may disappear but it often leaves an imprint of permanent RPE hypopigmentation (Fig. 8) with associated fluorescein angiographic transmission hyperfluorescence. Small granular subretinal deposits are associated with a favourable prognosis (Perkins et al. 2002), probably because they signify a short duration of detachment (Wang et al. 2005). Notably, chronic detachments with subretinal deposits leave highly visible imprints (Gismero et al. 2003). Long-standing serous detachment of any type may be followed by attenuation of the RPE corresponding to the detachment, and it may persist after resolution (Wang et al. 2002). Subretinal fibrosis can arise as a consequence of CNV (Fig. 11) or independently of neovascularization, as a result of severe fibrinous deposition (Fig. 12). The fibrinous material may play a role in anchoring a partly detached retina to an underlying pigment epithelial detachment (Hussain et al. 2006) (Fig. 5).

Fluorescein angiography

The diagnosis of classic CSC can often be made without fluorescein angiography, but angiography is a critical element in the differential diagnosis, notably of subretinal neovascularization, and in the planning of treatment. The diagnosis of CSC should not be made in the absence of fluorescein angiographic RPE abnormalities. These can range from a single clearly demarcated focus of RPE translucency and leakage to extensive areas of irregular hypopigmentation and fluorescence-blocking elements with or without true pigmentation. Non-pigmented elements that block choroidal fluorescence often display marked autofluorescence (Framme et al. 2005).

A prominent angiographic characteristic of CSC is that of an expanding point of fluorescein leakage under a serous detachment of the sensory retina, without signs of subretinal neovascularization (Fig. 4) (Robertson 1986). Usually, one or two leakage points are seen. The site of leakage is often hypopigmented, showing transmission of choroidal fluorescence. The hypopigmentation of the RPE is not associated with choriocapillaris atrophy or geographic atrophy of the RPE. Most leakage points are located within 0.5–1.5 mm of the centre of the fovea (Spitznas & Huke 1987). Less than 10% of cases demonstrate leakage in the foveal area. The most common location of leakage points is the superonasal quadrant of the posterior pole. The serous detachment may involve the site of leakage in CSC but often the two are not visibly connected. In a minor fraction of cases – 7% in one study (Spitznas & Huke 1987) and 25% in a study of acute cases only (Yamada et al. 1992) – the leaking dye is seen to stream upwards from the site of hypopigmentation in a ‘smokestack’ pattern (Fig. 5). It rises vertically to expand laterally at the top of the subretinal cavity in a mushroom- or umbrella-like fashion. It is unknown whether the flow is caused by a temperature gradient, by a density gradient existing between the newly secreted fluid and surrounding fluid that has been in the subretinal cavity long enough to have cooled or to have come hyperdense because of preferential resorption of water and small solutes. In other cases of CSC, multiple distinct foci of hyperfluorescence are present, yet none of them demonstrate expanding fluorescence (minimally enlarging spot configuration) whence it is difficult or impossible to attribute the serous detachment to a specific subset of leakage points. Finally, some cases show partial confluence of multiple irregularly distributed patches of hypopigmentation (multifocal ink-blot-like leakage) (Fig. 6). This order of listing is believed to reflect the development of fundus changes over time in non-resolving CSC. The number of RPE lesions and the configuration of lesion clusters are highly variable, ranging from a single focal lesion in one eye only to multiple clusters of lesions in both eyes. Pigment epithelial detachments are occasionally seen in CSC, as isolated lesions or adjacent to areas of mottled RPE, suggesting the presence of occult CNV (Fig. 7).

Hyperpigmentation is seen more rarely in CSC; it should be distinguished from subretinal deposits associated with angiographic choroidal shadowing (Figs. 6 and 8) (Iida et al. 2002). Such deposits appear to be prominent in CSC arising during pregnancy (Sunness et al. 1993).

The area of detachment in relation to the area of leakage is higher in smokestack cases than in pin-point leak cases without the smokestack phenomenon (Friberg & Campagna 1989). Assuming that the extent of the detachment is proportional to the rate of leakage, this is evidence that smokestack cases leak faster than other lesions. Particularly high rates of leakage appear to be associated with RPE detachments with a tear at the edge, the fluid leaking through this opening into the subretinal cavity. In one third of the cases, the point of leakage is in the papillomacular bundle, most commonly above the horizontal raphe (Wessing & Meyer-Schwickerath 1971).

Autofluorescence fundus photography

The autofluorescence characteristics of the fundus in CSC are clearly different from healthy eyes. In acute CSC, hypoflourescence has been demonstrated at the very point of leakage (Eandi et al. 2005). Acute CSC that has persisted for some time often shows granular or semi-confluent hyperfluorescence throughout the area of detachment (Fig. 9). In chronic CSC, irregular patterns of mixed hyper- and hypofluorescence can be seen (Framme et al. 2005; von Ruckmann et al. 2002). After reattachment, the autofluorescent subretinal deposits disappear slowly over a period of several months (Fig. 9).

OCT

OCT can demonstrate shallow serous detachments that are difficult to diagnose using slit-lamp biomicroscopy (Wang et al. 1999). OCT is also useful in determining whether reattachment has occurred after treatment. Especially in chronic cases, OCT is useful because morphological and functional restitution may be incomplete, thus providing little clinical guidance (Hee et al. 1995). Recent use of three-dimensional OCT has revealed small pigment epithelium detachments (PEDs) in 13 out of 29 patients with active CSC; two of the 29 patients having RPE detachments larger than 0.5 disc diameter (van Velthoven et al. 2005). Multiple PEDs can be found in some cases, usually located superior to the neurosensory detachment.

Electrophysiology

Focal electroretinography (ERG) has demonstrated reduced photoreceptor function of the detached retina in CSC (decreased amplitude and increased latencies of the b-wave, decreased oscillatory potentials) (Papakostopoulos et al. 1984; Miyake et al. 1988; Shiroyama & Miyake 1990). Multifocal ERG (mfERG) has demonstrated variable degrees of dysfunction outside the area of detachment (Marmor & Tan 1999) but normal function outside the area of visible fundus involvement (Vajaranant et al. 2002). Obviously, the delineation of past detachment is often uncertain. Subclinical fellow-eye involvement is suggested by the finding of abnormally low mfERG amplitudes (Dohrmann et al. 2001), but the patient having had subclinical transient detachment in the fellow eye cannot be excluded. Electro-oculography and ERG have not shown signs of RPE dysfunction in CSC (Gupta & Marmor 1995).

Acute CSC

Typical acute CSC is characterized by a duration of symptoms and/or retinal detachment of less than 6 months and monofocal or paucifocal fluorescein angiographic RPE leakage (Eandi et al. 2005). Large pigment epithelial detachments can be seen in a small fraction of patients with CSC – probably less than 5% (Castro-Correia et al. 1992; van Velthoven et al. 2005). Occasionally, the PED may rupture (Shanmugam & Bhende 2000), in which case pronounced angiographic ‘blow-out’ leakage through the rip can be observed.

Chronic CSC

Chronic CSC, which is also known as diffuse retinal pigment epitheliopathy, is generally characterized by multifocal, irregularly distributed and often widespread RPE changes associated with varying degrees of low-grade leakage (Cohen et al. 1983; Beuchat et al. 1988; Yannuzzi et al. 1992; Otsuka et al. 2002). The relation to acute CSC is documented by published cases of long-term follow-up (Castro-Correia et al. 1992; Bujarborua 2001; Katsimpris et al. 2006). Chronic CSC is more often bilateral and may occasionally present with gravitational tracts (Brancato & Bandello 1991; Bujarborua 2001; Gismero et al. 2003), a term used for oblong, vertical patches of RPE hypopigmentation that extend inferiorly from the macula. Presumably, gravitational tracts are produced by subretinal fluid of high specific gravity sinking toward the inferior fundus and dissecting its way through the subretinal space. CSC with inferior retinal detachment and/or tracts of attenuated RPE pigmentation is also called atypical CSC. In a study that recalled 50 out of 150 patients 3 years after their first visit, diffuse epitheliopathy had developed in eight patients (Castro-Correia et al. 1992). The extent of RPE attenuation on fluorescein angiography has been found to be predictive of subsequent visual outcome (Bandello et al. 2000, 2001). Retinal abnormalities also described in CSC include pigment migration, capillary teleangiectasia and capillary non-perfusion in the detached retina.

Sequels of CSC, inactive CSC and CNV

In the absence of retinal detachment, the diagnosis of CSC – or rather sequels of CSC – relies upon the history (which may or may not be informative) and on finding RPE lesions characteristic of CSC. The diagnosis should not be made in the absence of fluorescein angiographic RPE changes. Lesions are often found in both eyes, but their distribution is not usually the same. A shallow relative scotoma may remain after resolution of CSC, occasionally with metamorphopsia (Natsikos & Hart 1980), mild dyschromatopsia, and reduced contrast sensitivity.

As with other lesions of the RPE and/or Bruch's membrane, subretinal neovascularization of choroidal origin may appear as a complication of CSC (10, 11) (Faurschou et al. 1977). CNV can arise at any time after CSC (Gomolin 1989) and usually does so long after the resolution of the acute disease. In older patients, CNV following CSC is often assumed falsely to be a manifestation of age-related macular degeneration (AMD), but it is worth recalling that the diagnosis of AMD cannot be made if the other eye is healthy and does not demonstrate drusen. If photocoagulation treatment has been used to treat active CSC, it will be difficult or impossible to determine whether the CNV arose as a complication of CSC or as a complication of photocoagulation (Schatz et al. 1977). However, the risk of CNV in CSC is low: one study reported a single case in 39 patients followed for an average 9.6 years (0.3% per patient per year) (Dickhoff et al. 1989); another study found that CNV developed in four eyes in three out of 51 patients followed over a mean of 34.7 months (2% per patient per year) (Bandello et al. 2001).

In severe CSC with subretinal fibrinous deposits, it appears that instead of resorption of the subretinal material a subretinal fibrotic scar may form directly without the involvement of subretinal new vessels (Fig. 12) (Schatz et al. 1995; Hooymans 1998).

Subretinal deposits in CSC

Subretinal material is frequently present in CSC, mostly as fine granules (Figs 8C and 11A) (Wang 2005), more rarely as confluent patches (Fig. 8B) with a more or less fibrinous appearance (Gass 1991). The amount of subretinal debris increases with the duration of symptoms (Wang 2005). The isolation of photoreceptor outer segment fragments (Matsuo et al. 1986) from the aqueous humor of patients with the Schwartz syndrome suggests that such fragments may be responsible for the granular subretinal deposits in CSC (Larsen et al. 2004; Wang 2005; Schwartz 1973). Schwartz syndrome is an open-angle intraocular hypertension syndrome with aqueous corpuscles that is unresponsive to glucocorticoid therapy occurring in patients with anterior retinal tears or ora serrata dialysis. Aqueous cells and ocular hypertension resolve shortly after repair of the retinal detachment.

Visual prognosis

Acute CSC that resolves spontaneously or following treatment has a good long-term prognosis for visual function (Wong et al. 2004). Chronic CSC frequently results in considerable irreversible visual acuity loss, despite some functional improvement early after reapposition of the retina and a subsequent phase of slow visual recovery (Dohrmann et al. 2001). Among 47 US Air Force aviators with CSC, 51% had recurrent episodes, 17% had bilateral disease and 13% underwent laser photocoagulation (Green et al. 1988). Eighty-six per cent attained a final visual acuity of 20/20 or better.

Recurrences develop in one third to half of cases after the first acute episode, 10% having three or more recurrences. About half of the patients experience recurrence within 1 year of the primary episode (Gass 1967; Ficker et al. 1988). Eyes with recurrent disease tend to have reduced final visual acuity, stereopsis, colour vision and central visual field function. Examples of persistent loss of acuity and attenuation of the retina have mainly been reported in chronically recurrent cases (Newman 2002; Wang et al. 2002).

Choroidal neovascularization

The presence of CNV is suggested by the presence of subretinal haemorrhage, hard exudate and visible new vessels on biomicroscopy or fluorescein angiography (Schatz et al. 1977). Some cases of CNV, especially occult-only CNV, may lack such signs of activity. A classic fluorescein angiographic criterion for defining occult CNV is circumscribed late-phase fluorescence that is more prominent than that of the optic disk. Cases of chronic CSC with RPE hypopigmentation and, possibly, choroidal vascular congestion come close to fulfilling this criterion and may be difficult or impossible to distinguish from occult CNV, although ICG angiography may be of some value.

AMD

The diagnosis of AMD requires the presence of drusen or the assumption that drusen were present but disappeared with the development of CNV or geographic atrophy. Unilateral CNV and a healthy fellow eye without drusen exclude the diagnosis of AMD (Schatz et al. 1992). Confluent drusen with RPE detachment, pseudovitelliform degeneration and pattern dystrophy are rarely associated with significant serous detachment of the neurosensory retina.

Hypertensive choroidopathy

Arterial hypertension can be accompanied not only by intraretinal vascular changes and optic disk oedema but also by serous retinal detachment and RPE lesions known as Elschnig spots. These are focal RPE hyperpigmentations 50–200 µm in diameter with a hypopigmented halo. The lesions are believed to be caused by choroidal ischaemia secondary to extreme vasoconstriction during arterial hypertension. The purported mechanism is very similar to that proposed for CSC. In this context, it is remarkable that CSC is associated only weakly with arterial hypertension (Haimovici et al. 2004) and that in CSC secondary to systemic glucocorticoid therapy, arterial hypertension is conspicuously absent (Chaine et al. 2001). Elschnig spots only develop in a fraction of patients with arterial hypertension and in a highly variable pattern, but with a propensity for being located above major choroidal vessels. These observations suggest that an idiosyncratic reaction in susceptible subjects is involved in producing focal choroidal ischaemia in both conditions.

Pigment epitheliitis

Acute retinal pigment epitheliitis is an entity that has been observed in healthy young adults who present with reduced visual acuity and a central scotoma. The characteristic macular lesions, discrete pigment clumps with surrounding hypopigmented halos that show hyperfluorescence without leakage on fluorescein angiography (Chittum & Kalina 1987), are indistinguishable from Elschnig spots. Acute retinal pigment epitheliitis was described before the advent of OCT.

Idiopathic polypoidal choroidal vasculopathy

Idiopathic polypoidal choroidal vasculopathy is characterized by polypoidal dilations of choroidal vessels, notably in the peripapillary area, with associated serosanguinous detachment of the RPE and the neurosensory retina. If fluorescein angiography is not diagnostic, indocyanine green angiography may be helpful in displaying the vascular polyps (Schneider et al. 2001; Stanga et al. 2003; Yannuzzi et al. 2000).

Isolated RPE detachment

Although not a common ophthalmoscopically visible component of CSC, RPE detachment may occur in CSC in the absence of CNV. This suggests that isolated RPE detachment, in the absence of serous neurosensory retinal detachment or other RPE lesions typical of CSC, could be a manifestation of CSC. Indeed, cases have been reported where such solitary RPE detachment converted spontaneously to monofocal classic CSC (Bandello et al. 2000; Gomez-Ulla et al. 2000). Additionally, ICG angiographic findings have been interpreted as suggesting that a pattern of choroidal venous dilation and leakage underlies both CSC and idiopathic RPE detachment (Giovannini et al. 1997; Gomez-Ulla et al. 2000). A few patients with idiopathic, multiple serous RPE detachments have been described in a clinicopathological study (Gass et al. 2005). Sporadic reports of successful elimination of RPE detachments following photocoagulation treatment may represent cases of CSC (Fig. 7).

Vascular disorders

Systemic inflammatory disease may be associated with CSC, which has been described in patients with systemic lupus erythematosus, polyarteritis nodosa, sclerodermia, dermatomyositis and relapsing polychondritis (Eckstein et al. 1993; Taga et al. 2001). Usually, it is impossible to determine whether the serous detachment is caused by inflammatory disease of the choroidal vessels or by systemic glucocorticoid treatment. Of particular interest is that severe arterial hypertension (Venkatesh et al. 2006), toxemia of pregnancy (Somfai et al. 2006) and disseminated intravascular coagulation (DIC) can present with a neurosensory retinal detachment. Endothelin-1 is a candidate mediator for the vasoconstriction that is an essential feature of these conditions (Asakura et al. 1992). These observations fit the concept that idiopathic CSC is caused by choroidal vasoconstriction, as described earlier, suggesting that serous retinal detachment in arterial hypertension, toxemia, etc. is a type of secondary CSC, as opposed to idiopathic or primary CSC.

Vogt–Koyanagi–Harada's disease

This posterior uveitis or panuveitis with exudative retinal detachment and disc hyperemia may have only posterior pole manifestations at presentation and the patient may fail to report prodromal central nervous system (CNS) symptoms. Vogt–Koyanagi–Harada's disease (VKH) is characterized by acute multifocal exudative posterior pole pigment epitheliopathy with serous detachment of the neurosensory retina (Read et al. 2000), often more extensive than in CSC. The multifocal RPE lesions are typically more numerous and more leaky than in CSC, the leakage coalescing over time to fill the subretinal space. Because early, aggressive systemic glucocorticoid therapy is believed to reduce the risk of complications and visual loss, early diagnosis is mandatory. The diagnosis is based on the ocular characteristics and the association with Asian, Middle Eastern or Native American ethnicity, concomitant or closely associated aseptic meningitis, inner ear symptoms, anterior uveitis, alopecia, poliosis, and vitiligo. A favourable response to systemic glucocorticoid therapy will support the theory that the condition is not CSC, whereas lack of response should prompt renewed diagnostic efforts. If serous retinal detachment develops in a patient with VKH during glucocorticoid treatment, the possibility of glucocorticoid-induced CSC should be considered (Schalenbourg et al. 2002).

Optic nerve pit with serous macular detachment

All patients who present with a serous detachment of the macula or maculoschisis should be examined for the presence of an optic nerve pit. This abnormality of the optic nerve is not associated with fluorescein angiographic leakage and may be more or less conspicuous, with or without a visible communication between the pit and the subretinal fluid.

Optic neuritis

Optic neuritis can result in complaints comparable to those of patients with CSC, but in optic neuritis there is often more prominent loss of colour saturation, brightness and contrast, including a sensation of greyness without the Troxler effect seen in CSC. Meta-morphopsia is absent in optic neuritis. An afferent pupillary defect is prominent in optic neuritis and often demonstrable with the Pulfrich test, whereas it is minimal or absent in CSC (Sadun 1990). During the acute phase, optic neuritis is associated with pain and tenderness, which are never seen in CSC. After the resolution of optic neuritis, visual dysfunction comparable to that seen in CSC may be found, with uncharacteristic dyschromatopsia and reduction of acuity and contrast. In contrast to CSC, there is often a residual relative afferent pupillary defect after optic neuritis, a visual evoked potential delay, and a reduced critical flicker frequency (Han et al. 1985).

Posterior scleritis

This painful condition may be associated with serous retinal detachment. Ultrasonography reveals posterior scleral thickening and fluid in the subtenonal space.

Inflammatory choroiditis

Multifocal choroiditis (Gass & Little 1995), uveal effusion syndrome, sympathetic ophthalmia (Gomez-Valcarcel et al. 2004) and other posterior pole inflammatory or infectious processes may be associated with serous retinal detachment. This is a characteristic of the active inflammatory stages of such diseases. Serous detachment is highly unlikely over a postinflammatory chorioretinal scar, unless CNV has developed. It is important to distinguish fluffy, elevated lesions and granulomatous choroidal lesions that leak fluorescein from the non-expanding hyperfluorescent lesions of chronic CSC, which are flat, except for the occasional PED. Systemic diseases associated with choroiditis include systemic lupus erythematosus and sarcoidosis (Eckstein et al. 1993; Cunningham et al. 1996). When considering the diagnosis of choroiditis, it should be remembered that recurrent or chronic CSC often leaves multifocal irregular changes in fundus pigmentation that may resemble sequels of inflammatory choroidopathy (Cunningham et al. 1996). When systemic glucocorticoid treatment has been used in the treatment of systemic inflammatory disease, it is our experience that the treatment is more likely than the disease to be responsible for the retinopathy (Fig. 6) (Bouzas & Mastorakos 1994; Gass & Little 1995). Discontinuation of glucocorticoid treatment may be followed by resolution of the retinal detachment in CSC, but this response is less certain if chronic CSC has developed. Although the association between hypercortisolism and CSC is clearly accepted, a survey of patients with Cushing's syndrome found evidence of past or present CSC in only 5% of cases (Bouzas et al. 1993).

When related to the use of exogenous glucocorticoids, CSC has a less prominent male predilection, presents more often a chronic or atypical form and is more frequently bilateral (Quillen et al. 1996; Bouzas et al. 2002). Glucocorticoids should not be used in the treatment of CSC.

Choroidal tumours

Inferior detachments of the neurosensory retina are a common feature in eyes with choroidal haemangioma, melanoma, or metastatic tumour (Haut et al. 1984). Serous detachment of the macula can also be seen in choroidal osteoma and leukaemic choroidal infiltration.

Counselling

Counselling should suit the condition and attitude of the individual patient. The interview should use neutral terms to prompt a general account of the patients well-being, rather than leading questions that incorporate terms such as ‘stress’. Sufficient counselling to reassure the patient and enable relevant action may follow from a simple explanation of the association between CSC and stress. Controlled trials or case observations on the effect of psychosocial therapy have not been published.

Adrenergic receptor inhibition

The relation to stress and adrenergic hyperactivity has prompted attempts at systemic treatment of CSC by antiadrenergic medication. An uncontrolled case series of patients treated using the betaadrenergic inhibitor metoprolol described a promising course in some patients (Avci & Deutman 2005), but the treatment has not been adopted widely. In an uncontrolled case series of 13 eyes with subtype-unspecified CSC treated with the beta-blocker metipranolol, two eyes had persistent detachment after 4 months of treatment (Chrapek et al. 2002). Another uncontrolled trial found no difference in the outcome between the non-selective beta-blocker metipranolol and the beta 1-selective blocker metoprolol; all patients (21 and 30, respectively) experienced remission within 3 months (Fabianova et al. 1998). In experimental adrenalin-induced CSC in animals, alpha-adrenergic blockade is more effective than beta-blockade (Yoshioka 1991), but sporadic therapeutic tests in humans have not led to any significant clinical use of this principle (Heinrich 1974).

Acetazolamide

Systemic acetazolamide treatment promotes the resorption of subretinal fluid and case reports suggest that it may reduce subretinal fluid in CSC (Gonzalez 1992). However, there is no evidence that treatment promotes healing of the RPE lesion, long-term preservation of visual function, or a reduced rate of recurrence.

Photocoagulation

Retinal photocoagulation treatment has been used for decades in the treatment of CSC (Kanagawa & Matsubara 1970; Watzke et al. 1974). Photocoagulation accelerates resolution of the detachment (Burumcek et al. 1997). A prospective study compared eyes with leaks smaller than 250 µm in diameter treated by argon laser photocoagulation, with sham photocoagulation or photocoagulation away from the site of leakage (Robertson & Ilstrup 1983). Treatment appeared to shorten the duration of detachment by approximately 2 months and to reduce recurrences within a follow-up period of 18 months from 34% to none. Other studies have found no evidence of effect on long-term visual acuity or the prevalence of chronic disease (Ficker et al. 1988; Gilbert et al. 1984). The most benefit of treatment appears to be earlier resolution of disease. A retrospective comparison of treated versus untreated cases over 11 or more years of follow-up found that six out of six patients who were treated had no recurrences whereas 32 untreated patients had 17 recurrences (Yap & Robertson 1996). Photocoagulation treatment is often successful in achieving retinal reattachment, but visual acuity fails to recover in about 10% of eyes (Yannuzzi et al. 1992).

A potential benefit of early resolution may be mediated by a lower rate of RPE degeneration in treated eyes (Fuhrmeister 1983). The demonstration that long-standing serous detachment is associated with retinal atrophy supports the theory that photocoagulation may benefit visual outcome, given that a low rate of complications can be achieved (Wang et al. 2002). The available data do not enable assessment of the long-term risk of CNV.

The photocoagulation treatment strategy is to apply laser energy so as to obtain a confluent coagulation of moderate intensity covering the site of leakage responsible for the foveal detachment. Argon laser photocoagulation or photocoagulation using another source of green light should be directed to the site of leakage, using spot sizes of 200 µm diameter, exposure times of 0.2 seconds and a light intensity that enables bleaching without whitening of the outer retina (Robertson 1986; Greite & Birngruber 1975). When multiple candidate lesions are present, the leakiest one should be treated first, provided that it is not under or very nearly under the fovea. Subfoveal lesions should probably not be photocoagulated because it entails a risk of damaging foveal photoreceptors and of inducing secondary subretinal neovascularization.

Unlike treatment of CNV, it does not appear that CSC treatment that is too mild to induce resolution cannot be corrected by a second treatment. Eyes that have undergone photocoagulation treatment demonstrate a risk of later development of subretinal neovascularization, an event that can also occur without photocoagulation (Kanyange & De Laey 2002). The more intense the photocoagulation, the higher is the risk of secondary CNV. The strategy described above is easily applicable in acute CSC, whereas identification of the site or sites of leakage responsible for detachment may be problematic in chronic CSC.

The available evidence suggests that retinal atrophy can be avoided if resolution of detachment can be obtained within 4 months of the onset of symptoms (Wang et al. 2002). In long-standing serous detachments, the retina may demonstrate pigment migration, capillary dilation and capillary non-perfusion, to the extent that atypical CSC has been described as pseudo-retinitis pigmentosa (Gass 1977). Because the relation between the onset of detachment and the onset of symptoms is often uncertain, earlier treatment may be warranted – especially if the presence of subretinal granular deposits suggests that the detachment has lasted longer than the duration of symptoms (Wang 2005). Further support for early treatment includes best-corrected visual acuity 20/40 or less and multiple recurrences (Robertson 1986). Complications of photocoagulation treatment are rare (Robertson & Ilstrup 1983), but the treatment should be used with caution. Early photocoagulation may be warranted by special occupational demands for binocular visual function.

The RPE lesion responsible for subretinal fluid accumulation may be located at a considerable distance from the fovea and even along the temporal vascular arcades (Fig. 8) (Bonamour et al. 1977). A subfoveal location is seen in 4% of cases (Bonamour et al. 1977). This is usually considered a contraindication for photocoagulation, although an anecdotal report suggests that subfoveal photocoagulation can be made without adverse effects if the fovea is detached when treatment is applied (Gartner 1987).

Lack of fluid resorption after photocoagulation should lead to suspicion that the serous detachment is caused by CNV rather than by CSC. Photocoagulation in itself may cause damage to Bruch's membrane and lead to the induction of subretinal neovascularization or the development of a classic CNV component by extension from occult CNV.

A single paper has reported better visual outcome in 15 patients treated by infrared 810 nm photocoagulation than in 15 patients treated by argon 514 nm laser photocoagulation (Verma et al. 2004). However, conclusive results have not been produced.

Transpupillary thermotherapy

A small non-randomized study of transpupillary thermotherapy (TTT) suggests that this treatment may accelerate the resolution of CSC, but long-term safety and efficacy are not known (Shukla et al. 2006).

Photodynamic therapy

Verteporfin photodynamic treatment (PDT) of chronic CSC has been described in uncontrolled case series. Resolution of serous detachment followed treatment in the majority of patients, as did visual improvement. No complications have been reported (Canakis et al. 2003, 2004; Cardillo et al. 2003; Valmaggia & Niederberger 2006; Chan et al. 2003a; Yannuzzi et al. 2003). PDT being a more recent therapeutic option, it has been used mainly in cases where it was thought wise to avoid photocoagulation because of a juxtafoveal or subfoveal location of the RPE lesion, lack of a clearly defined leakage hotspot, concern about the potential induction of CNV or suspicion that CNV was already present. Under these circumstances, PDT has also been followed by a favourable course in nine cases of acute CSC (Ober et al. 2005). In 18 patients with chronic CSC, use of half-dose PDT also appeared to be effective (Lai et al. 2006); similar findings have been reported for the mechanistically comparable ICG photothrombosis technique (Costa et al. 2002). The use of half-dose verteporfin or 50% reduced light fluence PDT is suggested as a precaution against permanent RPE or choriocapillaris damage.

The treatment of subfoveal CNV secondary to CSC has never been the objective of a controlled clinical trial. PDT is widely favoured, by extension of the experience with AMD-related CNV and numerous case reports of a favourable outcome with lasting resolution of fluid and visual improvement often following only a single treatment (Canakis et al. 2003; Chan et al. 2003b; Ergun et al. 2004).

A controlled trial of PDT in chronic CSC would involve the problem of differentiating chronic CSC alone from chronic CSC with occult CNV. ICG angiography may demonstrate CNV in some otherwise questionable cases, but the false-negative diagnostic rate is unknown. The issue is complicated because all major studies of occult CNV have applied treatment only to occult CNV with activity in the form of subretinal haemorrhage, hard exudate or recent visual loss, the rationale being that occult CNV of lesser activity grades cannot reliably be distinguished from other causes of sub-RPE hyperfluorescence on fluorescein angiography. Resolution of intraretinal and subretinal fluid after PDT may be attributable, theoretically, to one or more of the known consequences of PDT: choriocapillaris photothrombosis, RPE damage or CNV closure.