Central serous chorioretinopathy

Introduction

Some of the clinical features of the idiopathic recurrent detachments of the macula have been known since 1866 when Von Graefe originally described the disorder he named relapsing central retinitis.1

Almost 100 years later, Bennet applied the term central serous retinopathy.2 At the same time, via the use of fluorescein angioscopy, Maumenee noted that the detachment of the macula resulted from a leak at the level of the retinal pigment epithelium (RPE).3 In the following years, numerous articles were published expanding our knowledge of the etiology, natural history, clinical manifestations, and treatment of this peculiar disorder.4-123 Since the disease appears predominantly to involve the choroid and, secondarily, the retina, the disorder is best termed central serous chorioretinopathy

(CSC).4

Pathogenesis

The pathophysiology of CSC is still not completely understood. The primary site of pathology begins with a disturbance of the RPE. Often, discoloration or elevation of the RPE is noted clinically. In turn, this leads to an alteration of the normally impermeable state of the RPE, leading to serous leakage underneath and through the RPE to produce a detachment of the neurosensory retina. It is difficult to accept that a single isolated disturbance of a few RPE cells may overwhelm the physiological pump of the neighboring normal RPE. Much more plausible is the assumption that there is a more diffuse dysfunction of the choroid to RPE as the basis of the disease.

In a series of patients with acute and chronic CSC studied with indocyanine green angiography (ICGA), Guyer et al. noted diffuse hyperpermeability around active leakage sites that were not appreciated on fluorescein angiography (FA).5 Furthermore, they described additional focal regions of ICG hyperfluorescence in clinically unaffected fellow eyes. Similar findings have also been described by Spaide et al. in a large series of patients with CSC.6 Interestingly, diffuse choroidal hyperpermeability was especially evident in older patients with chronic disease. It was seen bilaterally, even in asymptomatic eyes without discernible clinical or fluorescein angiography abnormalities. The cause of the choroidal abnormality is still unknown, but there are both clinical and experimental models suggesting that this diffuse hyperpermeability could be initiated by an abnormality of the autoregulation of the choroidal blood flow.

In 1927, Horniker first suggested the psycho- genic-related hypothesis of CSC.10 Clinically, CSC is more frequent among subjects with type A per- sonality.7-9 Type A behavior has been associated with the increased basal levels and release of cathecolamine and cortisol in response to stress.124 Although the role played by those substances in CSC is not well understood, cortisol excess may cause increased capillary fragility and hyperpermeability, which in turn may lead to choroidal circulation decompensation and leakage of fluid into the subretinal space.125 Furthermore, the anti-inflammatory properties of steroids may cause delayed healing of the RPE defect. By suppressing synthesis of extracellular matrix components and inhibiting fibroblastic activity, cortisol may also directly damage the RPE cells or their tight junctions, thus delaying any reparative process in the damaged RPE

cells.126-128 Finally, by its direct effect on ion transport, cortisol may be responsible for the reverse polarity of the RPE cells, causing them to secrete ions into the subretinal space. In turn, the ions may cause osmotic fluid attraction and serous macular detachment as a result of increased fluid inflow.

131 This hypothesis, implicating a disturbance in the autoregulation of choriocapillaris blood flow linked to abnormal circulating levels of cathecolamine or cortisol, is supported by experimental CSC animal models.

Another possible theory suggests that a protracted circulatory disturbance in the microcirculation of the choriocapillaris leads to increased fluid leakage in the sub-RPE space. To start with, the RPE cells are able to maintain their integrity and function, as well as being able to pump in a retinal-cho- roidal direction, thus keeping the subretinal space dry. However, the prolonged excessive stress on the RPE cells ultimately causes generalized damage to the cells and loss of function. A combination of the increased fluid leakage from the choriocapillaris on one side and the impaired function of the RPE cells on the other ultimately leads to pooling of fluid in the sub-RPE space, loss of continuity of the RPE layer, and pinpoint leakage of fluid in the subretinal space. The loss of function of the contiguous RPE cells allows the fluid to accumulate in the subretinal space and causes a neurosensory detachment. When new RPE cells substitute the damaged ones, there is spontaneous healing and reabsorption of fluid. Perpetuating microcirculatory disturbance leads to new damage and recurrence of the process. Further clinical and pathological studies are required to support the above-mentioned hypothesis further; yet, this theory provides an excellent explanation for some of the clinical characteristics of CSC: diffuse choroidal hyperpermeability in areas that appear clinically normal, recurrence of the disease, progressive damage to the RPE layer, and multifocal pinpoint areas of leakage in the more severe and chronic forms of CSC.

Clinical features

Demographics

Greater understanding of the clinical manifestations of CSC has considerably changed our knowledge of the demographics of the disease. Until a few years ago, CSC was considered predominantly a disease of males aged between 30 and 50 years. No case of CSC in a patient under the age of 20 years has been reported in the literature, the only exception being a seven-year-old girl who evidentially have had posterior scleritis.32 The overall incidence in males versus females in numerous reports is approximately eight or nine to one,2,33-40 but the incidence in women is noted to double between the ages of 31 and 40 years compared to between the

ages of 21 and 30 years.41 Duke-Elder and Dobree felt it was appropriate to diagnose the condition in patients under the age of 50 years, since, in patients over 50 years of age, distinguishing CSC from some forms of age related macular degeneration (AMD) would be extremely challenging.42-44 Very little is known about the age-specific prevalence and the clinical findings of CSC in older adults. In fact, neurosensory macular detachment in an adult over the age of 50 years suggests the presence of choroidal neovascularization (CNV) secondary to AMD, which is the most common cause of blindness in older adults.141 In 1996, Spaide et al. reported a study conducted on 130 older patients with neurosensory macular detachment.6,45 Over half the subjects were 50 years of age or older and 57 were diagnosed with CSC after they had turned 50. The male:female ratio in the study population was 2.6:1.0, with no significant differences among the age groups. Thus, although still typical of young adult males, CSC could also be manifested in females and older adults.

Risk factors

It has been speculated that psychological factors might play a causative role in CSC. Type A behavior and its psychological consequences, most notably, a sympathetic discharge, can adversely stimulate the eye as an organ system and the macula as an ultimate target area.7 Werry and Arends used the Minnesota Multiphasic Personality Inventory (MMPI) to compare patients with CSC with an ageand sex-matched group of healthy individuals.52 They found that patients with CSC showed significantly higher values on the hypochondria and hysteria scale. Another risk factor is the refractive state of the eye. Most CSC cases are diagnosed in patients with no refractive errors or a mild degree of hyperopia.7,53,54 There may also be a racial predisposition, with a higher incidence among Caucasians, Hispanics, and possibly Asians, and an extremely low occurrence in African-Ameri- cans.7,46,55-57 The more severe form of CSC occurs most frequently in individuals from south Asia or in those of Latin origin.34

Severe forms of CSC have been associated with pregnancy, end-stage renal disease (ESRD),18,73,74 organ transplant,17,19 increased endogenous cortisol production (Cushing’s disease),11,12 the use of inhaled nasal corticosteroids,20 systemic corticosteroid treatment, and epidural corticosteroid injection.75 We have seen one patient with ESRD treated with systemic corticosteroid who developed a severe, bilateral variant of CSC, complicated by bilateral giant rips of the RPE and permanent loss of vision. Serous retinal and RPE detachments resembling CSC have also been described in three patients with paraproteinemias and in a patient using methylenedioxymethamphetamine (MDMA) or ‘ecstasy’.76,77

There is a number of systemic diseases characterized by ischemic disorders of the choroid which may present with PEDs and bullous neurosensory detachments resembling CSC, such as systemic lupus erythematosus (SLE),142-150 polyarteritis nodosa,151,152 Goodpasture’s syndrome,153 Wegener’s granulomatosis,154 accelerated hypertension,155-157 toxemia of pregnancy,158-160 disseminated intravascular coagulopathy (DIC),161-163 and thrombotic thrombocytopenic purpura (TTP).152 It is difficult to judge whether the disease, its treatment, or both, cause CSC. Although these diseases have different pathogenesis and systemic manifestations, they all can produce serous retinal detachments. We think that the final common pathway is ischemia of the choriocapillaris caused either by vasospasm (e.g., malignant hypertension, toxemia of pregnancy), intravascular deposition of clots (e.g., DIC, TTP) or intravascular precipitation of circulating immunocomplexes (SLE and other collagen vascular diseases). The choriocapillaris ischemia may finally lead to damage of the retinal pigment epithelium and subretinal fluid exudation.

Symptoms

If the neurosensory detachment does not involve the central macula, the patient is usually asymptomatic and the detachment may resolve spontaneously. When the neurosensory detachment involves the fovea, the patient becomes symptomatic. Many patients first notice a minor blurring of vision, followed by the various degrees of metamorphopsia, micropsia, chromatopsia, central scotoma, loss of contrast sensitivity and increasing hyperopia. Usually, the area of metamorphopsia is reproducible on Amsler grid testing. Delay recovery to light stimulation detectable with the Photo Stress Test can also occur. Visual acuity in the acute stages ranges from 20/20 to 20/200.58,59 Vision can usually be improved with a small hyperopic correction. In some patients, the onset of symptoms is preceded or accompanied by migraine-like headaches.33

Examination

The anterior segment and vitreous remain normal. Biomicroscopic examination with a fundus contact lens reveals a macular neurosensory detachment. The detached neurosensory retina is usually transparent and of normal thickness. A yellowish discoloration is sometimes discernible in the foveal area, caused by increased visibility of the macular xanthophyll pigment. Multiple white-yellowish dotlike deposits cover the posterior surface of the retinal detachment in some cases (Fig. 1). A small serous pigment epithelium detachment (PED) may be present under the superior half of the neurosensory macular detachment. The PED appears as a round or oval area of detached RPE, yellow or gray in color, usually not larger than one-fourth of a

disc diameter. Long-standing and recurrent PEDs may present with pigment migration or atrophy. The pigment clumping may produce a cruciate or triradiate pigment figure. Although PEDs are usually small in CSC, some patients may develop one as large as a disc diameter, or even more. In these cases, the PED appears as a dome-shaped, well delineated, gray-yellowish elevation. A pink halo may surround the PED, caused by shallow separation of the retina at the edge of the PED. Some clinical findings help in differentiating a larger PED from a neurosensory detachment. Usually, the PED is better delineated, surrounded by a light reflex, and does not allow appreciation of details of the underlying choroid when compared to a neurosensory detachment. Sometimes, two or more PEDs are present, and, in some cases, the PED is noted above the neurosensory detachment, due to gravity forcing the fluid inferiorly. In this situation, there appears to be a lack of continuity between the PED and the neurosensory detachment (Fig. 2).

Although the subretinal fluid is usually transparent and allows clear visualization of the underlying RPE and choroidal details in some patients, it may also be cloudy and white-grayish in color, presumably because of the presence of fibrin exudation (Fig. 3).34 There must be significant hyperpermeability of the choriocapillaris, which allows a large molecule (fibrin, 340,000 Daltons) exudate in the extravascular space. It is possible that these patients have a blow out of the RPE at or near the border of the RPE detachment, allowing the abnormal egress of fluid and protein under the retina (Fig. 4).61 The subretinal fluid becomes progressively more opaque with increasing concentration of fibrin. Sometimes, there is a dark spot inside or on the edge of the fibrinous plaque which corresponds with the PED causing the RPE leakage. The fluid leaking from the choriocapillaris has a very low concentration of fibrin molecules, and thus it is transparent. The clear fluid leaking in the subretinal space allows a clear view of the underlying RPE detachment, which is usually reddish or dark in contrast to the surrounding cloudy subretinal fluid. While, in most cases, the fibrin deposit simply disappears, in a few cases, it might stimulate subretinal fibrosis and scar formation. This may cause permanent visual loss and become complicated by subretinal neovascularization and RPE rips.60,61 The conditions predisposing to subretinal fibrin exudation include large and multiple PEDs, chronic and recurrent disease, pregnancy,24 systemic corticosteroid use, organ transplant, diabetes, and male gender. In patients with chronic subretinal fluid, it is also possible to observe subretinal lipid deposition.61,62 Since subretinal lipid deposits are more typical of conditions causing chronic subretinal exudation such as AMD and polypoidal choroidal vasculopathy (PCV), it is important to recognize that they may also be present in CSC, and do not represent an exclusion criterion to the diagnosis of CSC as once was believed.

Clinically-discernible, peripheral-dependent bullous neurosensory detachments have been described in patients with CSC (Fig. 5).62-70 Yannuzzi et al. first characterized the presence of the RPE atrophic tracts extending inferiorly in the fundus periphery, secondary to the antecedent retinal detachment in patients with CSC.62 Presumably, there is a particularly severe and/or prolonged time leakage of fluid from an RPE defect in the subretinal space at the posterior pole. The subretinal fluid gravitates inferiorly to form a dependent neurosensory detachment in a ‘flask’, ‘teardrop’, ‘dumbbell’, or ‘hourglass’ pattern. Sometimes, the tract of subretinal fluid connecting the macular detachment with the bullous neurosensory detachment in the inferior hemisphere is so shallow that it is very difficult to appreciate. The RPE under the chronic retinal detachment experiences atrophic changes that appear as atrophic RPE tracts connecting the posterior pole with the dependent retinal detachment. The retina itself develops secondary manifestations, including pigment migration, capillary dilatation (telangiectasia) proximally, and capillary nonperfusion (is-

chemia) distally, to the area of detached retina. The changes in the RPE consist of both atrophy and pigment clumping in the form of perivascular deposits or bone spicules, the condition described by Gass as “pseudoretinitis pigmentosa-like atypical CSC presentation”.69

Angiography

Fluorescein angiography

The typical angiographic finding, occurring in about 95% of all cases of CSC, include the presence of one or more leakage point in the RPE. In the majority of these cases, the dye spreads to all sides slowly and evenly, staining the subretinal blister. Even though the initial diffusion of the dye occurs rather quickly, it may not reach the borders of the blister until the late phases of the angiogram. Interestingly, no diffusion or staining of the retina beyond the edges of the detachment is observed.

In 7-20% of all cases, the dye enters the blister

through a single leakage point, but, instead of spreading evenly to all sides, it first ascends in a so-called ‘smokestack’ phenomenon. Upon arrival at the upper limit of the blister, it expands laterally in a mushroomor umbrella-like fashion (Fig. 6).36-38 Shimizu and Tobari, who first described this phenomenon, believe that it is due to an osmotic pressure gradient resulting from different protein concentrations in the content of the blister and

in the liquid entering through the leakage point.78 There are usually one or two leakage points, but there may be as many as seven or more.35,36,38 In some rare cases, the mechanical defect at the margin of the PED may be apparent as a puncture or ‘blow out’. Large PEDs with multiple points of ‘blow out’ at their margin have also been described.79

Although usually the exudate extends into or be-

yond the fovea, it is interesting to note that the leakage point is found in the foveal area in less than 10% of all cases; as a matter of fact, it is more frequently located in a 1-mm-wide ring-like zone immediately adjacent to the fovea.80,81 The incidence rapidly decreases beyond this ring. The greatest overall incidence of leakage point is in the upper nasal quadrant, followed by the lower nasal quadrant, upper temporal quadrant, and lower temporal quadrant.2,38-40 These topographic differences are unexplained, since neither the neurosensory retina nor the neighboring structures, such as RPE, Bruch’s membrane, or choriocapillaris, show any regional differences that might account for this phenomenon. In 18-30% of cases, the leakage point lies in the area of the papillomacular bundle where the incidence above the midline is almost twice that below this line.2,38-40

Interestingly, the exudate tends to extend into and to involve the fovea, even if the leakage point is located eccentrically. This may be explained by the fact that, in the fovea, the rods, and thus the strong adhesion between neurosensory retina and RPE, are missing.80 In some cases, no leakage point is seen under the retinal detachment. In these cases, the area superior to the macular detachment should be studied because gravity may have caused the leaking point to remain outside the detached area. In

other cases, the leaking point cannot be found because the area has healed.

Indocyanine green angiography

The application of ICGA to the study of CSC has expanded our knowledge of the disease.5,6,82-95 The common findings in patients with CSC are multifocal areas of hyperfluorescence in the early and mid phases of the study, which tend to fade in the late phases (Fig. 7). Typically, these areas of hyperfluorescence are found, not only in correspondence with the leaking point seen on FA, but also in fundus areas, which appear clinically and angiographically normal, as well as in normal fellow eyes (Fig. 8). The areas of early hyperfluorescence are believed to represent diffuse choroidal hyperpermeability. On wide angle ICGA, we have been able to note multifocal hyperpermeable areas and presumed ‘occult’ PEDs, which extend far beyond the posterior pole.94 Although further pathological correlations are necessary, these findings suggest that PEDs may be much more common in CSC than previously believed. In addition, PEDs may be found in eyes that seem inactive on clinical examination and on FA. Both the multifocal hyperfluorescent spots seen throughout the fundus and the presumed occult PEDs that are only noted on ICGA

emphasize the fact that this disease may be more diffuse and widespread than previously believed.

Optical coherence tomography

Optical coherence tomography (OCT) is another

diagnostic tool for high-resolution cross-sectional imaging of the retina. It is useful for the quantitative examination of patients with central serous chorioretinopathy and for objectively monitoring the clinical course of the serous retinal detachment in this disease.166 Typically, in the acute phase of

Fig. 6. A 41-year-old male with the diagnosis of CSC in both eyes for ten years presented complaining of a sudden decrease of vision in the left eye. G. Mid-phase fluorescein angiography study of the fellow eye showing window defect hyperfluorescence corresponding to the RPE tract that extends inferiorly. Note a pinpoint nasal leakage superior to the nerve (white arrow).

CSC, patients present with thickening of the retina and areas of low reflectivity localized within the detached retina. Sometimes, it is also possible to detect a moderately reflective mass bridging the detached neurosensory retina and RPE, which seems to be a fibrinous exudate that accumulates in the subretinal space and infiltrates into the outer retina (Fig. 9).165 In patients who develop chronic CSC, OCT is extremely helpful in detecting shallow detachments and intraretinal cystoid spaces.

Natural history

When left alone, CSC generally heals spontaneously within 12 weeks, with complete recovery of visual acuity. However, recurrences are frequent and occur in about one-third to one-half of all patients after the first episode of the disease, and 10% of all affected individuals have three or more recurrences.4,33,38 In almost half the patients with recurrent disease, the recurrence occurs within one year of the primary episode, but relapses may occur up to ten years later.96,97

Although long-term follow-up data from patients with CSC are not available, there is evidence that even a single episode may be followed by a chronic, slowly progressing disturbance of the retinal pigment epithelium in the posterior pole. Some eyes may suffer from persistent and progressive macular detachment with the associated visual decline. A small percentage of patients will develop CNV, perifoveal RPE atrophy, choriocapillaris atrophy secondary to the RPE damage in the areas of RPE tracts, and subretinal lipid deposition.71 This severe variant of CSC appears to be more frequent in patients of Latin or Asian ancestry, and is usually associated with frequent recurrences, permanent

central vision loss, and significant superior visual field loss.

Other complications noted in these patients are cystoid macular edema (CME) and cystoid macular degeneration (CMD). Intraretinal cystoid spaces detected by OCT but without intraretinal leakage, or CMD, was a common finding in eyes with chronic CSC and reduced central vision after resolution of subretinal fluid. Chronic foveal detachment and antecedent intraretinal leakage were proposed to be the mechanisms for the development of these changes. In conjunction with foveal atrophy, CMD was an important clinical finding to account for the poor visual outcome in patients with CSC.

Differential diagnosis

Although the clinical diagnosis of CSC is usually confirmed by fluorescein angiography, several entities should be considered in the differential diagnosis.

Infectious and inflammatory disorders

Similarly to CSC, Harada’s disease may present with serous macular detachments. The presence of anterior uveitis, vitritis and optic disc hyperemia, the associated systemic manifestations, and the prompt response to anti-inflammatory therapy, are helpful in differentiating Harada’s disease from CSC. Posterior scleritis can also present with exudative neurosensory detachment at the posterior pole, but it can be distinguished from CSC by the presence of scleral thickening, vitreous cells, and pain on ocular movements. The diagnosis can be confirmed on ultrasound examination by the presence of an echolucent area at the posterior pole behind the echo of the sclera (T sign, typical of posterior scleritis). Sympathetic ophthalmia may also present with serous macular detachment, but the associated intraocular inflammation, yellowish cellular detachments of the RPE (Dalen-Fuch’s nodules), and the history of trauma to the fellow eye allows easy differentiation of the two diseases. Two additional conditions, which may present with exudative neurosensory macular detachment in otherwise healthy subjects, are idiopathic uveal effusion syndrome and benign reactive lymphoid hyperpla-

sia.138-140

Tumors

Choroidal melanoma, choroidal hemangioma, choroidal metastasis, choroidal osteoma, and leukemic choroidal infiltrates can present with the exudative macular detachments. While clinical examination of the fundus is usually sufficient for recognizing the choroidal tumor, some tumors, especially choroidal hemangiomas, can be confused with large PEDs with associated neurosensory detachment. In

these cases, ultrasound examination and angiography may be helpful in determining the correct diagnosis.

Vascular disorders

Collagen vascular disease such as SLE, polyarteritis nodosa, scleroderma, dermatomyositis, and relapsing polychondritis, may be associated with the serous detachments of the macula caused by fibrinoid necrosis of the choroidal vessels. In these diseases, CSC may arise as a result of the prolonged systemic use of corticosteroids. Malignant hypertension, toxemia of pregnancy, and disseminated intravascular coagulopathy, can present with a neurosensory detachment secondary to acute multifocal occlusion of the choroidal arteries and choriocapillaris, and necrosis of the overlying RPE (Elshing’s spots).

Optic nerve pit with serous macular detachment

Clinically, a pit should be looked for in all patients with CSC. On FA, there is no pinpoint leakage of the dye or slow filling of the macular detachment as seen with CSC. OCT may be helpful in imaging the schisis-like separation of the retinal layers at the posterior pole and the presence of the optic disc pit or any other optic nerve abnormalities, which can lead to a neurosensory detachment.164

Optic nerve sheath meningocele

Optic sheath meningocele is a rare disease. The term ‘optic sheath meningocele’ was recently proposed by Garrity and Forbes to describe primary CSF cysts of the optic nerve sheath, without apical mass or malformation of the cranio-orbital junction.167 Presenting symptoms are often related to involvement of the optic nerve, with a slow or rapid decrease of visual acuity. Sometimes there is also a serous macular detachment, simulating CSC. CT

and MRI studies reveal a tubular-cystic enlargement of the optic nerve/optic sheath complex, with thickening of the optic nerve. Radiological differential diagnosis should include optic nerve tumors,

such as gliomas, meningiomas, and arachnoid cysts involving the optic nerve sheath.167

Age-related macular degeneration

The differentiation between age-related macular degeneration (AMD) and CSC is necessary when CSC is present in adults over 50 years of age. While FA is helpful in distinguishing the two conditions when there is well-defined CNV secondary to AMD and a well-defined pinpoint leakage in CSC, it is much less helpful in the presence of diffuse, ill-defined hyperfluorescence, which may be caused by both occult CNV or a diffuse ‘ooze’ of RPE. In such cases, ICGA may be helpful in showing multifocal early hyperfluorescence, fading in the late phase in CSC, and late hyperfluorescence, corresponding to the CNV in AMD.5

Polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy (PCV) is presumed to be a variant of occult CNV. The typical or classic clinical presentation of PCV poses little challenge. However, an isolated macular variant may have clinical and FA characteristics resembling CSC (Fig. 10). These atypical cases of PCV involve small-caliber vascular abnormalities and may present exclusively with detachment of the neurosensory retina. The polypoidal lesions may clinically and fluorescein angiographically resemble small PEDs. These cases of PCV may masquerade as CSC (Fig. 11).98

Vitelliform macular detachment

Patients with cuticular or basal laminar drusen and vitelliform foveomacular or pattern dystrophy may present with visual loss caused by yellow serous exudative detachment of the retina in the macular area in one or both eyes. These neurosensory macular detachments, which resemble the lesions seen in Best’s vitelliform dystrophy, may be mistaken for serous detachments of the RPE. Fluorescein angiography is helpful in differentiating these conditions from CSC. In the early phases of the study, the yellowish subretinal fluid obstructs the fluorescence of the underlying choriocapillaris, while later there is patchy filling of the subretinal fluid with dye through the RPE defects.

Treatment

Although, thus far, no medication has proven effective in CSC, and the disorder generally resolves spontaneously, a beneficial effect of photocoagulation has been shown in several studies.2,99,103-115 Some authors have also reported that treatment of CSC with photocoagulation reduces the recurrence

rate,97,106,114,115 whereas others109,110,116-118 have ob-

served no such difference.

Because CSC is usually a self-limiting disease, and there are possible complications associated

with laser treatment, particularly when applied very close to the fovea, the recommendation for photocoagulation therapy can only be based on clinical judgment. As a general rule, we recommend observing any new onset of acute serous macular detachment for the first three months, unless the patient has special occupational reasons, which require rapid improvement of visual acuity, or if the affected eye is the only eye. If the detachment does not resolve itself after the first three months, and the leakage point is remote from the center of the fovea, it is reasonable to treat a symptomatic patient. If the leakage point is within 500 µm from the center of the fovea, six months of observation is recommended before undertaking treatment. Other indications for laser treatment are primary detachment with visual decline in a patient who has experienced permanent visual loss from an untreated macular detachment in the fellow eye and recurrent macular detachment in the eye that has experienced permanent visual loss from the initial episode. Furthermore, laser treatment is indicated in particularly severe forms of CSC, which are known to have poor prognosis if left untreated, such as CSC complicated by multiple serous detachment of the RPE and bullous sensory retinal detachment, dependent neurosensory detachment, epithelial tracts, diffuse RPE decompensation, subretinal deposits of fibrin and lipids, and those associated with secondary CNV.

A recent fluorescein angiogram showing the area of RPE leakage should be positioned in a viewer for guidance at the time of laser treatment. A fundus contact lens is used for examination of the posterior pole and for laser treatment. While the laser is in standby, the point of fixation is identified by asking the patient to fixate on a target light and to hold the fixation while the target light is moved (either the smaller light beam of the slit lamp or the laser aiming beam are appropriate). Once the fixation point has been clearly identified, the RPE leakage point to treat is identified with the help of the fluorescein angiography picture (known fundus landmarks, such as foveal avascular zone and vessel crossing sites, are used to define the exact position of the area to be treated).111,113 The spot size should be slightly larger than the leaking point, usually 200 µm. Although, for very small leaks, just one spot may be sufficient, more laser spots (three to five) are usually necessary to complete the treatment. It is better to start the treatment with a low intensity (100 mW) and a relatively long duration (0.2-0.3 seconds), and to use a slight increase of intensity if necessary, looking for a slight gray discoloration of the treated area. The laser beam is focused at the level of the RPE in order to obtain a slow, mild intensity burn, the goal of treatment being a faint gray discoloration of the RPE and not a frank white reaction, as in laser treatment of CNV. After laser photocoagulation treatment of the leak, anatomical resolution of the

macular detachment generally occurs in about two weeks in uncomplicated cases, but it may require up to six weeks in longstanding detachments with turbid subretinal fluid. Complete visual recovery usually requires twice that time. In chronic, severe forms of CSC, there is usually diffuse decompensation of the RPE, which appears on FA as multifocal pinpoint areas of leakage or diffuse ‘ooze’ of the RPE. In such cases, even if its value has not been proved in clinical trials, there is a rationale for applying a grid of laser treatment to cover the area of RPE decompensation completely.

Complications

Although rare, there are some recognized complications in laser treatment of CSC, the worst of which is inadvertent photocoagulation of the fovea. The patient should always be informed that a persistent scotoma corresponding to the site of laser photocoagulation might be experienced after treatment. Secondary choroidal neovascularization may be induced by the laser treatment, especially when excessive intensity is used.103,109,119,120 An often underestimated complication is the slow but progressive enlargement of the area of RPE atrophy caused by the laser treatment. When the treatment site is close to the center of the fovea, the enlargement of the RPE scar may eventually involve the fovea and cause delayed irreversible visual loss. Whenever possible, the laser treatment of a leaking point in CSC should be avoided within the foveal avascular zone.

Recently, there have been case series reports on the use of photodynamic treatment (PDT) with verteporfin for chronic CSC. The rationale behind such a therapeutic approach is that of causing a reduction of blood flow in the choriocapillaris, which is hyperpermeable in CSC.121-123 This therapeutic approach would appear to be promising for chronic and recurrent cases of CSC, especially when there is diffuse decompensation of the pigment epithelium.

Conclusions

Although the etiology of central serous maculopathy is not entirely clear, its pathogenic mechanism is supposed to disturb the choriocapillaris and blood flow, leading to a choroidal exudate, and to pigment epithelium detachment, resulting in local disruption of this structure, and to fluid leakage under the sensory retina. The application of indocyanine green shows multifocal areas of hyperfluorescence in the early and mid phases, which tend to fade in the late phase. Optical coherence tomography (OCT) is an important tool for the high resolution of this disease. Although, thus far, no medication has proven effective in central sero ma-

culopathy, and the disorder generally resolves spontaneously, a beneficial effect of photocoagulation has been demonstrated.

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