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Central serous chorioretinopathy is a retinal disorder characterized by localized serous detachment of the macula. It is secondary to retinal pigment epithelial decompensation and choroidal vascular changes. Most of the cases resolve spontaneously and gain normal vision. Some cases are non-resolving and require treatment. Such chronic cases, if not treated, will lead to permanent loss of vision. This activity reviews the evaluation and treatment of central serous chorioretinopathy and highlights the role of the interprofessional team in the care of patients with this condition. Objectives: Describe the etiology of central serous chorioretinopathy. Explain the typical presentation of central serous chorioretinopathy. Review the typical imaging findings and treatments associated with central serous chorioretinopathy. Summarize the importance of collaboration and communication amongst the interprofessional team to improve the outcome of patients affected with central serous chorioretinopathy. Access free multiple choice questions on this topic.

Central serous chorioretinopathy (CSCR) is a retinal disorder characterized by localized serous detachment of the macula with or without focal serous pigment epithelial detachment (PED). It is mostly seen in young men aged 20–45 years.[1] Albert V Graefe first described this condition as central recurrent retinitis in 1866. Bennet coined the term “central serous retinopathy,” and Gass described the pathogenesis.[2] The patient complains of distorted images, the apparent small size of objects, and blurred vision. Most of the cases resolve spontaneously in 3-6 months.[3] For non-resolving cases, treatment includes laser photocoagulation and photodynamic therapy.[4][5] AntiVEGF and mineralocorticoid receptor antagonists have also been tried.[6][7][8]

Yannuzzi suggested a relationship between CSCR and type A personality.[9] These persons are aggressive, competitive, and have a sense of urgency. Such behavior causes catecholamine release, which increases choroidal permeability.[10] Psychological stress and depression also predispose to CSCR.[11] A definite association exists between CSCR and exogenous corticosteroid use.[12][13] It is generally associated with systemic intake, either oral or intravenous.[13][14] But studies have reported CSCR after nasal spray, topical skin creams, intra-articular, epidural, or periocular use.[15] CSCR has also been reported following kidney, heart, and bone marrow transplantations.[16][17] Increased endogenous cortisol production, such as Cushing disease and pregnancy, increases the risk of CSCR.[18] Steroid-effect might be an idiosyncratic response that affects vascular autoregulation. Drugs other than corticosteroids that have been associated with CSCR are oral MEK inhibitors phosphodiesterase inhibitors pseudoephedrine oxymetazoline[17][19][20][21] Association between H. pylori infection, peptic ulcer disease and CSCR has been reported in some studies.[22][23] It is associated with stress and sleep disturbances. Treatment of the underlying cause resolves CSCR.[24][25][26] Familial association of CSCR has been reported.[27][28][29] Single nucleotide polymorphisms in complement factor H and cadherin 4 is thought to be associated.[15] CSCR associated pachychoroid can be inherited as a dominant trait.[30][31] Other systemic associations of CSCR include Sleep apnea syndrome Systemic hypertension Psychopharmacologic medications Systemic lupus erythematosus[32] Gastroesophageal reflux disease[24]

CSCR is the fourth most common retinal disorder threatening the vision.[33] Men are commonly affected. The male-female ratio was found to be 6:1 in a population-based study.[34] The mean age group is 39-51 years.[34][35] When females are affected, the age is usually higher than males. It is generally unilateral. However, bilateral involvement may be in up to 40% of cases.[36] However, the majority of cases have pigment epithelial detachment (PED) in the fellow eye also. Bilateral changes in the choroid are usually noted on optical coherence tomography (OCT)[37] and indocyanine green angiography (ICGA).[37] Kitzmann et al. found the incidence of CSCR to be 9.9 cases per 100,000 population.[34]

The pathophysiology of CSCR is multifactorial, which causes retinal pigment epithelial (RPE) disturbances and circulatory changes in the choroid.[38] There is choroidal inflammation, which causes stasis and ischemia.[22][38][39] The choroidal vessels become hyperpermeable, and the choroid becomes thickened. This leads to increased tissue pressure, which disturbs the anatomic integrity of RPE and causes PED. The micro-defects in the RPE hamper its barrier functions. The choroidal fluid crosses the RPE and cause neurosensory detachment. It gets collected in the subretinal space. Another hypothesis is the loss of polarity of RPE.[40] Normally, the RPE keeps the retina in a dehydrated state by pumping out fluid from the subretinal space to the choroid. With the loss of polarity, the pumping reverses and fluid is directed towards the subretinal space. The non-perfusion in the choriocapillaris may lead to the widening of venous channels and increased hydrostatic pressure.[22][39] The mineralocorticoid receptor pathway has also been implicated. Experiments have shown that intravitreal injection of aldosterone causes dilatation of choroidal veins and congestion, which leads to the accumulation of fluid in the subretinal space.[41] The widespread choroidal hyperpermeability can be seen with indocyanine green angiography (ICGA).[38] Enhanced depth imaging optical coherence tomography (EDI-OCT) has demonstrated increased choroidal thickness and congestion.[42] On ICGA, areas of choroidal staining adjacent to the site of RPE leakage have been shown.[43][44]

The patient complains of unilateral blurred vision, micropsia, metamorphopsia, relative scotoma, and color vision disturbances. There is temporary hyperopia. Vision ranges from 6/9-6/60, though in most cases, it is better than 6/12. On examination, there is a well defined circular or oval area of neurosensory detachment over the posterior pole. Occasionally, a yellowish feathered-edge subretinal material (presumably fibrin) and PED may also be seen.[45] The acute episode generally resolves within 3 to 6 months. If fluid persists beyond this period, it is called “chronic CSCR.” It is generally seen in older patients or those receiving long term corticosteroids.[11][46] Atypical CSCR presents as inferior bullous retinal detachment. Such cases may be associated with multifocal PED, multifocal neurosensory retinal detachments, and multiple leaks on fundus fluorescein angiogram (FFA).[47]

Ancillary tests OCT (optical coherence tomography) This is the first line of investigation. The presence of subretinal fluid (SRF) is characteristic of CSCR. The resolution of SRF can be documented on serial OCT. Sometimes band-like fibrin deposits can be seen in the subretinal space.[48] Outer retinal dipping may be noted, which may touch the RPE or a PED.[49] The area of retinal dipping/sagging may denote the location of the leak.[49] In chronic CSCR intraretinal cystic changes, hyperreflective dots and elongated photoreceptor outer segments may be present. CSCR is currently considered as part of the pachychoroid spectrum. Thicker choroid has been demonstrated on EDI OCT in eyes with CSCR and fellow eyes. Dilatation of outer choroidal vessels and thinning of choriocapillaris is present.[14][18][50][51] PED is commonly seen. It is contiguous to areas of choroidal hyperpermeability, as evident on ICGA. Sometimes a double layer sign can be seen in chronic CSCR.[52] However, this sign is typically seen in idiopathic polypoidal choroidopathy (IPCV). IPCV and CSCR constitute the pachychoroid spectrum and ICGA helps in differentiating the two. Tiny white dots may be seen in CSCR on ophthalmoscopy, which appear as hyper-reflective dots in the outer retina on OCT. Fundus autofluorescence (FAF) In acute CSCR, focal areas of hypo-autofluorescence are seen that may correspond to the leak on FFA. In chronic CSCR, hyper-autofluorescent tracks are present due to the accumulation of photoreceptor pigments. Fundus fluorescein angiography (FFA) Three types of fluorescein leakage patterns are seen in CSCR- inkblot, smokestack, and diffuse. In the inkblot pattern, pinpoint leakage occurs in the early phase, which then concentrically enlarges in the late phase. In smokestack pattern, the leakage starts as a pinpoint and gradually expands to form an umbrella-like (or tree-like) appearance. Inkblot pattern is more common. In the diffuse leak, there are multiple small/inconspicuous leaks in a localized area, which cause an increase in the size and intensity of the area of hyper-fluorescence. In chronic CSCR, patchy areas of hyper-fluorescence are seen corresponding to areas of RPE atrophy. Serous PED shows early hyper-fluorescence with a progressive increase in the intensity, but size remains the same. Indocyanine green angiography (ICGA)

Three types of fluorescein leakage patterns are seen in CSCR- inkblot, smokestack, and diffuse. In the inkblot pattern, pinpoint leakage occurs in the early phase, which then concentrically enlarges in the late phase. In smokestack pattern, the leakage starts as a pinpoint and gradually expands to form an umbrella-like (or tree-like) appearance. Inkblot pattern is more common. In the diffuse leak, there are multiple small/inconspicuous leaks in a localized area, which cause an increase in the size and intensity of the area of hyper-fluorescence. In chronic CSCR, patchy areas of hyper-fluorescence are seen corresponding to areas of RPE atrophy. Serous PED shows early hyper-fluorescence with a progressive increase in the intensity, but size remains the same. Indocyanine green angiography (ICGA) ICGA is helpful in imaging the choroidal vasculature. It shows hypocyanescence in the early phase denoting choriocapillaris nonperfusion and delayed filling. In mid-phase, hypercyanescence is seen, indicating choroidal vessel hyperpermeability. This hypercyanescence slowly fades in the late phase.[21][22][29] These changes are bilateral. ICGA also helps in the detection of a choroidal neovascularized membrane (CNVM) in chronic CSCR, which may occur in up to 23% of cases.[22][53] OCT angiography (OCTA) It is useful in detecting CNVM in chronic CSCR by a non-invasive method. It shows dilated choriocapillaris in most eyes with CSCR.[34] Abnormal choroidal flow patterns suggestive of choroidal ischemia with surrounding hyperperfusion are seen in acute and chronic CSCR.[35] Dilated choroidal vessels are detected as high flow, well-delineated channels.[46] The SRF is seen as dark areas at the level of choriocapillaris. The PED is detected as dark spots. OCTA is being increasingly used to identity CNVM in CSCR and may detect CNVM in up to 20% cases of chronic CSCR.[53]

The majority of cases of CSCR resolve spontaneously, so observation is done for 3-6 months.[22] In some cases, CSCR persists beyond 6 months or recurs. Chronic CSCR leads to macular degeneration, foveal atrophy, and RPE changes. In these cases, active treatment should be initiated.[54] If the patient is on steroids for a medical condition, then they should be discontinued and alternative therapy should be taken if possible. As CSCR of long duration may cause an irreversible visual decline, some clinicians may plan to treat early. Usually, for the first episode of CSCR, most clinicians observe (with reduction of stress/stoppage of steroids or other predisposing factors) for the initial few months as more than 80% cases resolve spontaneously. Indications for early intervention include Visual demand of profession (pilot) or the patient for early recovery Recurrent disease Severe decline of vision in the other eye due to chronic CSCR Laser photocoagulation: The RPE leakage sites, as seen on angiography, can be treated with laser photocoagulation. Such therapy seals the leakage point and hastens the resolution of subretinal fluid.[55] The thermal laser is indicated for extrafoveal leakage points. A green-wavelength laser produces a light gray scar over the focal RPE leak. Spot size is 100 micrometers, duration ≤0.1-second, and power ranging from 70-120 milliwatts is used. It should be applied judiciously as it may cause scotoma and laser-induced choroidal neovascularization.[55][56][57] The laser does not reduce the chances of recurrence. To overcome these problems, a micropulse laser can be used.[58][59][60][61] It is a diode or yellow laser which emits micropulses and delivers subthreshold laser energy without a visible burn. This stimulates the surrounding RPE cells and seals the defect. Some studies have reported faster visual recovery with this therapy.[62] Photodynamic therapy (PDT)

The RPE leakage sites, as seen on angiography, can be treated with laser photocoagulation. Such therapy seals the leakage point and hastens the resolution of subretinal fluid.[55] The thermal laser is indicated for extrafoveal leakage points. A green-wavelength laser produces a light gray scar over the focal RPE leak. Spot size is 100 micrometers, duration ≤0.1-second, and power ranging from 70-120 milliwatts is used. It should be applied judiciously as it may cause scotoma and laser-induced choroidal neovascularization.[55][56][57] The laser does not reduce the chances of recurrence. To overcome these problems, a micropulse laser can be used.[58][59][60][61] It is a diode or yellow laser which emits micropulses and delivers subthreshold laser energy without a visible burn. This stimulates the surrounding RPE cells and seals the defect. Some studies have reported faster visual recovery with this therapy.[62] Photodynamic therapy (PDT) CSCR with a subfoveal leak, juxtafoveal leak, multiple leaks, and chronic cases with diffuse decompensation of RPE are better managed with PDT. PDT causes vascular remodeling of the choroid and choroidal hypoperfusion.[63][64] A drug called verteporfin is injected intravenously, which then reaches the eye. The verteporfin is activated by a laser on the source of leakage. This seals the RPE defect. It may also prevent future recurrences in some eyes. It appears to be a more effective treatment with a lower complication rate. Using EDI-OCT, the choroid can be monitored for thinning after treatment with PDT.[4] Low fluence PDT has improved efficacy and safety profile in chronic CSCR cases.[65][66] Anti-vascular growth factor (VEGF): Anti VEGF therapy has been proposed to reduce choroidal hyperpermeability. They upregulate the tight junctions between endothelial cells and the reduction of vascular fenestrations.[67][68][69] Various studies have reported the effect of bevacizumab, ranibizumab, and aflibercept on CSCR.[70][71][72] Results remain inconclusive, and long term benefits warrant more studies. There is no level 1 or level 2 evidence for the use of anti-VEGF agents in CSCR though they have a definite role in CSCR related choroidal neovascularization or IPCV, which is a close differential diagnosis. Anti-corticosteroids

Anti VEGF therapy has been proposed to reduce choroidal hyperpermeability. They upregulate the tight junctions between endothelial cells and the reduction of vascular fenestrations.[67][68][69] Various studies have reported the effect of bevacizumab, ranibizumab, and aflibercept on CSCR.[70][71][72] Results remain inconclusive, and long term benefits warrant more studies. There is no level 1 or level 2 evidence for the use of anti-VEGF agents in CSCR though they have a definite role in CSCR related choroidal neovascularization or IPCV, which is a close differential diagnosis. Anti-corticosteroids Patients with CSCR commonly have endogenous hypercortisolism, thus drugs targeting cortisol pathways might be effective.[73] Ketoconazole is an antifungal agent which has anti glucocorticoid effects. It blocks the conversion of cholesterol to androgenic glucocorticoid end-products. Few studies have investigated ketoconazole as a treatment for CSCR without any significant benefit.[74] Mifepristone (RU-486) is an abortifacient agent. Its mechanism of action is mediated through its glucocorticoid and progesterone receptor antagonistic effects. It has been used in chronic CSCR patients with varied responses.[75] Finasteride is a weak anti-androgen that works through inhibiting type II 5 alpha-reductase that is necessary for converting testosterone to dihydrotestosterone (DHT), a potent androgen. It has been investigated in CSCR, but more trials are needed to evaluate the effect.[76] Eplerenone, a selective aldosterone-receptor antagonist and potassium-sparing diuretic, was originally approved in 2002 by the FDA for the treatment of hypertension. The medication is generally well-tolerated, but drug interactions must be ruled out prior to initiation, and serum potassium and blood pressure must be monitored during treatment. Studies have shown it to improve visual acuity and decrease central macular thickness in a small series of patients with chronic CSCR.[77][78][79][80] Currently, its use in CSCR remains investigational and is not considered standard of care. Further studies are warranted to further clarify the role of aldosterone receptor antagonists in CSCR. A randomized control trial could not find the superiority of eplerenone to placebo in improving vision in chronic CSCR, and the authors recommended against its use for this indication.[81]

Eplerenone, a selective aldosterone-receptor antagonist and potassium-sparing diuretic, was originally approved in 2002 by the FDA for the treatment of hypertension. The medication is generally well-tolerated, but drug interactions must be ruled out prior to initiation, and serum potassium and blood pressure must be monitored during treatment. Studies have shown it to improve visual acuity and decrease central macular thickness in a small series of patients with chronic CSCR.[77][78][79][80] Currently, its use in CSCR remains investigational and is not considered standard of care. Further studies are warranted to further clarify the role of aldosterone receptor antagonists in CSCR. A randomized control trial could not find the superiority of eplerenone to placebo in improving vision in chronic CSCR, and the authors recommended against its use for this indication.[81] Rifampicin is an anti-tuberculous medication that facilitates the catabolism of endogenous steroids. It increases the cytochrome P-450 content in the liver, thus affecting the metabolism and bioavailability of endogenous corticosteroids, consequently aiding in the resolution of CSCR and improving its symptomatology.[82][83][84] However, care is to be taken as hepatotoxicity can develop as a side effect while being treated for CSCR. Adrenergic blockers As CSCR is closely associated with type A personality, which is characterized by high adrenergic activity, it was proposed that blocking adrenergic receptors might have a positive effect on CSCR.[84] It has been shown that CSCR patients who were diagnosed with hypertension and were started on metoprolol, a beta-blocker, had improved clinically.[85][23] [85]However, further assessment of the actual role of adrenergic blockers needs to be tested. Anti-Helicobacter pylori treatment The therapy of Helicobacter pylori-related peptic ulcer disease has shown variable results in CSCR.[23] However, peptic ulcer disease may be looked for in patients with chronic CSCR, and its management adds to the available therapy for chronic CSCR.

Other diseases of choroid and retina can closely mimic CSCR. They are ARMD (age-related macular degeneration), IPCV, and optic disc pit associated maculopathy. ARMD is seen in patients above 50 years. Chronic CSCR can develop secondary CNVM on follow up or after laser photocoagulation. OCT angiography is helpful in delineating the neovascular complex of ARMD. EDI OCT shows thicker choroid in CSCR and thin to normal choroid in ARMD. IPCV produces serous macular detachment and RPE changes similar to CSCR. The polyp and branching vascular network are characteristic findings on ICGA. OCT typically shows serosanguinous or notched PED. Optic disc pit causes serous macular detachment at the macula. On careful slit-lamp biomicroscopy, focal excavation can be seen on the temporal part of the optic disc. Retinal schisis is commonly observed in optic disc pit, while these changes are infrequently seen only in chronic CSCR. The sub-internal limiting membrane cavity after the resolution of sub-internal limiting membrane hemorrhage (including after Valsalva retinopathy) may simulate CSCR on cursory examination.[86]

Chronic CSCR cases, if not treated, can have complications. Chronic CSCR with PED can develop RPE rip with secondary exudative retinal detachment. Such patients complain of sudden diminution of vision. Other complications can be CNVM and macular degeneration. Diffuse retinal pigment epitheliopathy in CSCR may be the cause of the irreversible visual decline.

Any patient presenting with CSCR should receive treatment by an ophthalmologist and an interprofessional team evaluation by primary clinicians and endocrinologists. Interprofessional communication can lead to better patient management. The patient will most often present to the primary clinician, and these professionals should be aware of the condition as it is treatable. Prompt referral to an ophthalmologist is necessary. These patients can then be followed by their primary clinicians and should ensure compliance with treatment. Pharmacists can ensure correct dosing on the medication management aspect of the condition. Nursing will be the first in the department to come in contact with patients on followup and can assess treatment progress as well as evaluate compliance with both medication and lifestyle measures, and report any issues to the primary care clinician. This collaborative, interprofessional approach to care can ensure optimal patient outcomes.