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CSCR Masquerades
C H A P T E R
15 CSCR Masquerades Niroj Kumar Sahoo, Sumit Randhir Singh, Jay Chhablani Smt. Kanuri Santhamma Centre for Vitreo-Retinal Diseases, L.V. Prasad Eye Institute, Hyderabad, India
INTRODUCTION Central serous chorioretinopathy (CSCR) is primarily a disease of the choroid that typically affects middle-age men, manifesting as a neurosensory detachment of the posterior pole with or without an associated pigment epithelial detachment. Various risk factors implicated in the pathogenesis of the disease include corticosteroid exposure, phosphodiesterase inhibitor use, obstructive sleep apnea, and Type A personality traits. In its acute form, it can manifest with a wide range of visual disturbances such as central scotoma, metamorphopsia, dyschromatopsia, and micropsia,1, 2 which typically resolves within 3–4 months with or without treatment, leaving only disturbances in color vision in some patients.3 The chronic form, however, can be unforgiving for the patient, with the eye presenting with varying degrees of retinal pigment epithelium (RPE) abnormalities, often culminating in moderate to severe vision loss because of RPE atrophy in the central macula, foveal atrophy, or cystoid macular degeneration (CMD) involving the fovea.4–8 Rarely, certain atypical forms can present without the classic predisposing risk factors or might be unresponsive to conventional treatment. It is these myriad of posterior segment findings that often pose a diagnostic dilemma, considering the fact that a number of retinal and choroidal conditions can mimic such findings and masquerade CSCR. It is not uncommon to see a patient being diagnosed with CSCR and mismanaged until a correct diagnosis has been reached. Similarly, certain atypical presentations of CSCR have misdiagnosed as other retinal or choroidal pathologies. In this chapter, we intend to summarize some of these puzzling conditions that might lead the ophthalmologist toward a diagnosis of CSCR and the features that can aid in better differentiation. A summary of the various conditions is shown in Fig. 1.
CSCR AS INITIAL DIAGNOSIS These conditions usually present with neurosensory detachment of the posterior pole with ill-defined leaks similar to CSCR. A detailed ophthalmic evaluation with multimodal imaging often is needed to reach a correct diagnosis (Table 1).
Central Serous Chorioretinopathy https://doi.org/10.1016/B978-0-12-816800-4.00014-0
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FIG. 1 Summary of an approach to a patient with subretinal fluid involving the macula.
Polypoidal Choroidal Vasculopathy (PCV)
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TABLE 1 Masquerades of Central Serous Chorioretinopathy (CSCR) CSCR as Initial Diagnosis
CSCR as Final Diagnosis
• Idiopathic choroidal neovascularization • Polypoidal choroidal vasculopathy • Retinal angiomatous proliferans • Cavitory optic disc anomalies including optic disc pit • Dome-shaped macula • Bilateral diffuse uveal melanocytic proliferation • Choroidal hemangioma • Bestrophinopathies • White dot syndrome
• Vogt-Koyanagi-Harada • Posterior uveitis • Tributary retinal vein occlusion • Uveal effusion syndrome • Idiopathic juxtafoveal telangiectasis • Posterior scleritis • Diabetic macular edema
IDIOPATHIC CHOROIDAL NEOVASCULARIZATION (CNV) Idiopathic CNV is primarily a disease of patients younger than 50 years and is characterized by development of CNV in the absence of pathologic myopia, angioid streaks, trauma, or any other inflammatory or hereditary disorders.9 It is most commonly a type 2 CNV.10 Lesions are usually small, well-defined, and extend above the RPE. Occasionally, it presents with a subretinal halo or pigmented plaque. Occasionally, the yellowish subretinal lesion in CNV can be confused with CSCR presenting with subretinal fibrin and vice versa. Dye angiography as a diagnostic tool often can be misleading, as idiopathic CNV also can present with an ink-blot type leak seen in CSCR. A CNV lesion should be suspected strongly in presence of subretinal lipid or hemorrhage, subretinal hyperreflective material, double-layer sign between RPE and Bruch’s membrane and interruptions in the RPE on optical coherence tomography (OCT).8, 11 Also, demonstration of the vascular network in idiopathic CNV by Fundus fluorescein angiography (FFA), Indocyanine green (ICG) or optical coherence tomography angiography (OCTA) often is diagnostic. Certain atypical type 2-like leaks have been demonstrated in CSCR, resulting from alteration in flow dynamics because of pigment epithelium detachment (PED) adherence to the retina.12 Finally, a CNV complex can be missed on OCT if the scan does not pass through the lesion. An illustrative case is shown in Fig. 2. CNV (especially type 1) arising in the setting of a chronic CSCR rarely can appear to be an idiopathic CNV on history and clinical examination as both the conditions can have pigment epithelial detachment, subretinal fluid, intraretinal fluid, cystoid macular degeneration, retinal atrophy, and diffuse irregular hyperfluorescence on angiogram.13 Careful examination of the OCT image is important in these cases, which reveal a thickened choroid in the former along with widespread RPE abnormalities. Idiopathic CNV usually responds to anti-VEGF (vascular endothelial growth factor) agents and has a better prognosis compared to neovascular age-related macular degeneration (AMD).14, 15 CNV secondary to CSCR, however, responds better with laser, photodynamic therapy (PDT), anti-VEGF agents, or a combination of the above.16–18
POLYPOIDAL CHOROIDAL VASCULOPATHY (PCV) PCV is a disease of the choroid and is believed to be a part of the pachychoroid spectrum of diseases. It typically affects older individuals in their fifth decade of life, and is characterized by reddish-orange, aneurysmal, or polypoidal lesion involving the posterior pole or
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FIG. 2 A 36-year-old man presented with diminution of vision in his right eye for 1 week. Fundus examination and optical coherence tomography showed neurosensory detachment of the macula (A, B) and inkblot leak pattern on fundus fluorescein angiography (C). A repeat scan through the leak site revealed the presence of a choroidal neovascular complex (D).
periphery. The classic presentation of a PCV lesion is a recurrent episode of exudative retinal detachment, subretinal hemorrhage, serous or hemorrhagic PED.19–21 However, it also can present with serous macular detachment associated with PED, which can give an impression of a CSCR.22–24 Similarly, neurosensory detachment along with subretinal or sub-RPE hemorrhage in a case of CNV secondary to CSCR can mimic a PCV lesion. Differentiating between these two entities becomes difficult in these circumstances because both conditions can present with a thickened choroid. A series of RPE changes seen in cases of CSCR often can mask an underlying PCV,22 and thus a PCV lesion always should be suspected in cases of nonresponding or persistent,25 and long standing CSCR.26 These lesions often are solitary and located at the margin or near the atrophic retina. The appearance of a PCV lesion in a case of CSCR often has led to the dilemma about whether these entities coexist in the same eye or whether CSCR, during the course of illness, transforms to PCV.26–28 In view to this observation, few studies have suggested a common pathogenesis of choroidal congestion and hyperpermeability for the two entities.29–31 Additionally, a PCV lesion has been described to be associated with arteriosclerotic changes32 and engorged vortex veins secondary to chronic choroidal venous congestion.33 ICG often is considered diagnostic in these lesions because it can delineate these polypoidal lesions (Fig. 3) and the branched vascular network in early phase associated with local pooling.
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Retinal Angiomatosis Proliferation (RAP)
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FIG. 3 A 60-year old woman presented with diminution of vision in the right eye for 1 year. (A) Optical coherence tomography revealed a large neurosensory detachment involving the macula with a pigment epithelial detachment. (B) Fundus fluorescein angiography revealed multiple small polyps (arrowheads).
RETINAL ANGIOMATOSIS PROLIFERATION (RAP) RAP represents a distinct form of occult CNV that typically affects individuals in their eighth decade of life. It develops from the paramacular intraretinal capillaries and characterized by development of retinochoroidal anastomotic vessels. It was first described by Yannuzzi and co-workers as a variant of exudative AMD (Type 3). Three stages of development have been described: Stage 1: Intraretinal neovascularization with intraretinal edema and hemorrhage.34 Stage 2: Subretinal neovascularization because of extension of the neovascularization posteriorly, characterized by localized retinal detachment, intraretinal, preretinal hemorrhage, intraretinal edema, and serous PED.34 Stage 3: Choroidal neovascularization characterized by a fibrovascular PED and a retinochoroidal anastomosis..34 FFA has limited diagnostic role and the leak pattern seen in stage 2 lesion can sometimes closely resemble that of a CSCR. Features that suggest the presence of a RAP lesion are the older age of presentation, presence of blood in the intraretinal or subretinal space, and the pattern of leak in late phase of ICG angiography. ICG demonstrates focal areas on hyperfluorescence (hot spots), which increase in size as the dye diffuses into the intraretinal and subretinal space.34
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CAVITORY OPTIC DISC ANOMALIES INCLUDING OPTIC DISC PIT (ODP) ODP is a congenital anomaly of the optic disc characterized by focal excavation. Although it most commonly involves the inferotemporal aspect of the disc, any quadrant of the disc can be affected. It occurs because of a defect in the closure of the superior end of the embryonic fissure. Clinically, it manifests with varying degrees of field defects and often is seen to be complicated by a maculopathy. Macular involvement is in the form of serous retinal detachment and presence of multiple schitic cavities in the outer retina. The presence of these features, along with a central or occult/invisible pit, can portray a picture that is exactly the same as a CSCR lesion.35 The source of fluid in these cases is poorly understood. It is believed to be because of the passage of liquefied vitreous into the intraretinal and the subretinal space following traction by a posterior vitreous detachment.36 Other sources include CSF from the subarachnoid space,37 blood vessels at the ODP,37 choroidal vasculature through Bruch’s membrane, and the RPE.38 Absence of leak in FFA and the characteristic changes in the optic disc help to differentiate it from CSCR. Presence of schitic cavities, extent of the subretinal fluid up to the disc margins, and outer lamellar hole on OCT are some of the features that favor the diagnosis of optic disc pit, even when the pit is clinically subtle.35 OCT sometimes demonstrates focal excavation of dysplastic retina into a defect in the lamina cribrosa (Fig. 4).39 Hyporeflective areas also have
FIG. 4 A 23-year-old man presented with diminution of vision in the right eye for 1 year. (A) Optical coherence tomography (OCT) revealed a neurosensory detachment involving the macula. (B) Fundus image showed grayish discoloration on the temporal aspect of the disc (black arrow). (C) OCT scan through the optic nerve head revealed an optic disc pit with underlying hyporeflective areas (white arrow).
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Dome-Shaped Macula (DSM)
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been described below the areas of excavation.40 Unlike acute CSC, which it resembles, treatment of optic disc maculopathy is indicated in most cases because of poor natural history41 and it responds to pars plana vitrectomy (PPV) with laser and gas injection.42
DOME-SHAPED MACULA (DSM) DSM is described as a dome-shaped forward macular bulge seen in eyes with high myopia presenting with or without a posterior staphyloma. Around 50% of cases present with a neurosensory detachment involving the macula.43 A localized increased scleral thickness and an abrupt change in choroidal thickness has been suggested to be the underlying mechanism behind formation of SRF.44, 45 The clinical picture often closely resembles the CSCR lesion because of the similar leak patterns on FFA and ICG. Features specific to DSM, however, include high myopia, the forward bulge of the macula on OCT, the presence of choroidal thinning, and subfoveal choroidal thickening. (Fig. 5) Incidence of CSCR, on the other hand, is considered very low in these myopic eyes46 probably because of the significantly thin choroid.47 Most cases of DSM usually resolve spontaneously, however, persistent cases respond to PDT or aldosterone antagonist.48, 49
FIG. 5 A 43-year-old man presented with features of serous neurosensory detachment in the left eye (A) with inkblot-type of leak on fundus fluorescein angiography (B) and was being treated as central serous chorioretinopathy elsewhere. (C) Optical coherence tomography revealed a dome-shaped elevation at the macula.
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BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION (BDUMP) BDUMP is described classically as a paraneoplastic syndrome of the eye often seen in patients with occult, but advanced, visceral malignancies, most commonly ovarian, lung, gall bladder, cervical, uterine, kidney, pancreatic, breast, esophageal, and colorectal cancers. The main clinical features are multiple, faint, red, round, or oval patches at the level of the RPE (giraffe-pattern); multifocal areas of early hyperfluorescence corresponding with the patches on FFA; development of multiple, slightly elevated, pigmented, and nonpigmented uveal melanocytic tumors, with diffuse thickening of the uveal tract; exudative retinal detachment; and rapid progression of cataracts.50 Fundus autofluorescence (FAF) shows hyperautofluorescence corresponding to faint red lesions and hypoautofluorescence pattern corresponding to areas of RPE atrophy.51 A subretinal fluid and irregular and thickened RPE can be demonstrated on OCT.51 Visual prognosis usually is considered very poor and treatment options are limited to corticosteroid, external beam radiotherapy, surgery, and treatment of the visceral malignancy.50, 52
CHOROIDAL HEMANGIOMA Choroidal hemangiomas are benign vascular hamartomas that can be either diffuse or circumscribed. A circumscribed choroidal hemangioma classically presents as an orange-red lesion associated with serous macular detachment. Occasionally, however, it can mimic a CSCR, especially when it presents in a middle-age adult with a macular detachment that is large enough to obscure the choroidal lesion. Ancillary tests often are needed in such cases to reach at a definitive diagnosis. FAF imaging shows hypoautofluorescence corresponding to the area of the lesion. A lacy hyperfluorescence in choroidal phase can be demonstrated on FFA, which increases through the remaining phases of angiogram. ICG better delineates the intrinsic vacularity and demonstrates a phenomenon of wash out that is seen as a hypocyanescent or isocyanescent area with surrounding staining.53 The choroidal mass can be detected by ultrasonography, which shows acoustic solidity in B-scan and high internal reflectivity in A-scan (Fig. 6). Newer imaging modalities such as EDI-OCT often demonstrate an increased choroidal thickness in these lesions. Although an increased choroidal thickness also is seen in CSCR, it is often in the range of 500 μm,2 whereas the thickness is often more than 1000–2000 μm in choroidal hemangioma.
BESTROPHINOPATHIES Bestrophinopathies encompass a clinical spectrum of inherited macular dystrophies that are caused by mutation of the BEST 1 gene expressed in the RPE. It includes Best vitelliform macular dystrophy (BVMD), adult-onset vitelliform macular dystrophy (AVMD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and autosomal recessive bestrophinopathy (ARB).54, 55 A diminution of central vision and a neurosensory detachment
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Bestrophinopathies
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FIG. 6 A 35-year-old woman presented with diminution of vision of left eye for 1 year. (A) Optical coherence tomography (OCT) revealed a neurosensory detachment. Careful fundus examination showed an orange-yellow elevated mass along the inferior arcade (B), which was confirmed by OCT (C). (D) Ultrasound B-scan imaging showed a mass in the posterior pole with acoustic solidity.
involving macula can be seen in all of these conditions. The subretinal deposits are seen on OCT as hyperreflective structures. This can simulate a CSCR presenting with subretinal fibrin. In certain cases, a clear subretinal fluid also can be present instead of these deposits, giving an impression of a CSCR. Also, the absence of the classical pseudohypopyon can further make the diagnosis more enigmatic. A ring of hyperautofluorescence can be seen in FAF in the areas of subretinal deposits as these are believed to be lipofuchsin precursors. Points in favor of bestrinopahthies, however, include a younger age group (although it can present as late as in the sixth decade in AVMD) and the characteristic clinical finding of bilateral, egg yolk-like round lesions affecting the macula..56 FFA demonstrates blocked fluorescence corresponding to the areas of subretinal deposits but also can show irregular hyperfluorescence. The diagnosis can be confirmed using EOG, which shows a decreased Arden’s ratio.57 A representative case is shown in Fig. 7. Examination of the family members, even when asymptomatic, can aid in the diagnosis without the need for the previously mentioned imaging modalities.
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(A)
(B)
(C) µV 1500
Minimum = 266 µV
1000
Maximum = 297 µV
500
Arden ratio = 112 %
0
0
(D)
5
10
15
20
25
mn
FIG. 7 A 35-year-old woman presented with history of diminution of vision in both eyes for 2 years. (A, B) Optical coherence tomography and fundus imaging revealed a neurosensory detachment. (C) Fundus autofluorescence showed punctate hyperautofluorescent spots at the margin of the lesion. (D) Electro-oculogram confirmed the diagnosis of Best disease that showed a decreased Arden ratio.
WHITE DOT SYNDROME (WDS) WDS is a heterogeneous group of multifocal inflammatory conditions characterized by multiple white-yellow lesions involving the outer retina, RPE, or choroid. It often is accompanied by a hyperpermeable choroid, which is responsible for its exudative manifestations. Serous macular detachment has been described with punctate inner choroidopathy (PIC) and acute posterior multifocal placoid pigment epitheliopathy (APMPPE).58, 59 Features that help in differentiating it from certain atypical forms of CSCR60 are the typical whitish-yellow lesions in the posterior pole and FFA showing early hypofluorescence
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Posterior Uveitis
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and late hyperfluorescence. Serous retinal detachment also has been described in cases of MEWDS.61 Finally, certain WDS-like serpiginous choroiditis, multifocal choroiditis and panuveitis (MCP), PIC, progressive subretinal fibrosis and uveitis (SFU), and multiple evanescent white dot syndrome (MEWDS) also have been described as being complicated by a CNVM that can mimic a CSCR. Angiogram is helpful in these cases to help delineate the neovascular membrane.
CSCR AS FINAL DIAGNOSIS Considering the wide range of manifestations seen with CSCR, especially the atypical forms, it is not uncommon to find a misdiagnosed and mismanaged case of CSCR. This often leads to exacerbation of the disease. Nonresponse to treatment or aggravation of signs should point toward a diagnosis of CSCR. Some of these conditions are described in Table 1.
VOGT-KOYANAGI-HARADA (VKH) VKH is a bilateral granulomatous panuveitis affecting young individuals, characterized by a diffuse choroidal inflammation with or without extraocular manifestations. It is one of the most common conditions that CSCR is misdiagnosed as, because both the conditions can present with thickened choroid, exudative retinal detachment, and pinpoint leaks on FFA (atypical CSCR). Because VKH is an inflammatory condition, it is marked by anterior chamber and vitreous cells and optic disc edema. These findings, however, are not seen in CSCR, because it is a disease of the intrinsic choroidal vascularity. Careful examination of various imaging modalities can reveal certain subtle signs that can help in differentiating between the two conditions. The pinpoint leak seen in VKH usually is associated with late prominent pooling in the area of SRF along with disc leak, while it is less leaky in CSCR. A diffuse choroidal hyperpermeability, hypofluorescent dark dots, and optic disc staining are characteristic of VKH on ICG,62 while the choroidal hyperpermeability usually is localized in CSCR.63 Also, speckled hyperautofluorescence corresponding to the leak points on FAF is a feature specific to CSCR.64, 65 The classic finding of increased RPE undulation index, RPE folds, fluctuation of ILM, and subretinal septa also have been described only with VKH, whereas, RPE hyperplasia and PED is seen more commonly with CSCR.66 An illustrative case is demonstrated in Fig. 8. On ultrasonography, a low to medium reflective choroidal thickening in the posterior fundus is typical for VKH. It is important to distinguish between the two entities because corticosteroids used in the treatment of VKH can lead to a worsening or lack of response in a case of CSCR.
POSTERIOR UVEITIS Posterior uveitis is a group of disorders having diffuse choroidal inflammation as a common underlying pathology. The incidence of CSCR seen in patients diagnosed with posterior uveitis is high, because of both misdiagnosis and use of steroids. Misdiagnosis of CSCR for posterior uveitis can lead to intensification of steroids, which can be devastating for CSCR.
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FIG. 8 A 44-year-old man presented with diminution of vision in both eyes for 1 month. Optical coherence tomography showed neurosensory detachment of the posterior pole with retinal pigment epithelium undulations (A). Multiple pockets of pooling and pinpoint hyperfluorescence were seen in fundus fluorescein angiography (B). A diagnosis of Vogt Koyanagi Harada syndrome was made.
Atypical CSCR presenting with yellowish subretinal fibrin, bullous exudative retinal detachment, and multifocal leaks on angiogram can closely resemble a choroiditis lesion. It is important to rule out signs of inflammation of posterior segment on biomicroscopy, FFA (disk leak, retinal vasculitis), or ICG (choroiditis or dark dots). Thus, a patient presenting with exudative retinal detachment, minimal signs of ocular inflammation, and nonresponse to steroids suggests a diagnosis of steroid-induced CSCR. Also, the presence of classical signs of diffuse exudative epitheliopathy, localized leak patterns, hyperpermeable choroidal vessels, and bilaterality, are more in favor of a CSCR.67 A placoid fundus lesion with subretinal fluid seen in ocular syphilis easily can mimic chronic CSCR with fibrin. These patients show prompt response to injections of penicillin.68
TRIBUTARY RETINAL VEIN OCCLUSION (TRVO) Retinal vein occlusion (RVO) is the second-most common vascular disease after diabetic retinopathy.69 The usual manifestation is a cystoid macular edema (CME) that results because
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Idiopathic Juxtafoveolar Retinal Telangiectasis (IJFT)
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of increase in vascular permeability. This is believed to be secondary to an increase in intravascular pressure resulting in dysfunction of the endothelial blood-retinal barrier.70 Although rare, the appearance of a neurosensory detachment has been proposed to be a result of traction on the muller cell cone by the expanding CME that breaks the ELM barrier.71 Signs that suggest a diagnosis of TRVO in a patient with SRD include flame-shaped retinal hemorrhages, cotton wool spots, and an occluded/sclerosed tributary retinal vein. Neovascularization and collaterals also can be seen in long-standing cases. FFA acts as a useful adjunct in the diagnosis because it helps to delineate the capillary nonperfusion areas and macular involvement in these patients. A relationship between risk of RVO and presence of CSCR also has been proposed.72
UVEAL EFFUSION SYNDROME (UES) Uveal effusion syndrome is a rare, ocular disorder that typically affects middle-age men, and is characterized by idiopathic serous detachment of choroid, ciliary body, and retina.73 The pathogenetic mechanism behind the development of the uveal effusion syndrome is believed to be a thickened sclera resulting from the accumulation of glycosaminoglycans.74 This decreases the trans-scleral movement of protein, which, in turn, results in accumulation of protein in the extravascular space. This change in the concentration gradient prevents the movement of fluid from the suprachoroidal space to the choroidal circulation, and a choroidal effusion ensues.52 Compression of the vortex veins and the resultant choriocapillary congestion is suggested to be another mechanism.75 The mechanism behind the formation of a retinal detachment is believed to be a decompensated RPE because of long-standing choroidal detachment. This can mimic a bullous variant of CSCR. A choroidal detachment observed both opthalmoscopically and on ultrasonography, however, clinches the diagnosis of UES. In addition, ICG shows diffuse granular choroidal hyperfluorescence in the early phase and classical leopard spots, which is in contrast to the focal leaks of CSCR.74 Nanophthalmos should be ruled out in these cases, which can manifest with a similar scleropathy.74
IDIOPATHIC JUXTAFOVEOLAR RETINAL TELANGIECTASIS (IJFT) IJFT refers to a heterogenous group of clinical conditions that is characterized by telangiectactic alteration of the juxtfoveal capillary network. It manifests as incompetence, ectasia, or irregular dilations of the capillaries in the juxtafoveolar region. Two distinct types have been described. MacTel type 1 is congenital and unilateral variant that presents with aneurysmal dilatation of the juxtafoveal capillaries. MacTel type 2 (most common) is an acquired, bilateral variant.76 Typical ophthalmoscopic findings include a right-angled vessel associated with pigmentation and a foveal atrophy on OCT. The appearance of subretinal neovascularization (SRNV) often is accompanied by a neurosensory detachment of the macula. This detachment, however, can occur even without the presence of a SRNV and can resemble a CSCR, because the telangiectactic vessels can be subtle/occult in certain cases of MacTel type 2.77, 78 Demonstration of these SRNVs and telangiectatic vessels on angiography usually makes the diagnosis clear. Coexisting CSCR and IJFT also have been described.79
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POSTERIOR SCLERITIS Posterior scleritis, a painful inflammatory condition of the posterior sclera, typically is seen in middle-age women, although any age group can be affected. It can be either idiopathic or associated with other conditions such as herpes zoster ophthalmic, herpes simplex, syphilis, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus, Wegener’s granulomatosis, polyarteritis nodosa, giant cell arteritis, ulcerative colitis, and Crohn’s disease.80, 81 Fundus usually shows choroidal folds, optic disk edema, serous retinal detachment and choroidal detachment. The degree of vision impairment depend upon the severity of macular involvement. Apart from the presence of a serous retinal detachment, several similarities exist between posterior scleritis and CSCR. These similarities include multiple pinpoint leaks on FFA and increased choroidal thickness on OCT. The presence of external manifestations such as hyperemia, proptosis, and painful eye movements (because of muscle involvement), however, rules out CSCR. Although not pathognomonic, demonstration of a T-sign on ultrasonography, which represents fluid collection in the sub-tenon’s space and the optic nerve sheath, with variable degree of thickening of choroid and sclera, favors the diagnosis of posterior scleritis (Fig. 9).
FIG. 9 A 27-year-old woman presented with diminution of vision in the right eye along with mild pain and redness. Optical coherence tomography revealed a bulge in the posterior pole (A). On ultrasound B-scan, fluid in the subtenon’s space and optic nerve sheath was seen (B).
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Diabetic Macular Edema
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DIABETIC MACULAR EDEMA Although uncommon, serous retinal detachment in DME has been reported in about 15%– 30% of eyes.82–84 The source of the fluid is believed to be a hyperpermeable retinal vasculature85 or the choroidal circulation.86 The presence of serous retinal detachment, however, is not related to the retinal thickness or the stage of DME.83, 87 It is important to look for the presence of features suggestive of diabetic retinopathy, such as microanuerysms, neovascularisation, and leakage from the retinal vasculature, which can be differentiated easily from the focal leaks at the level of RPE in CSCR on FFA. Presence of shallow subretinal fluid and a thickened choroid should raise the suspicion of CSCR (Fig. 10). It is not uncommon, however, to see both the conditions coexisting in the same patient. Leaks from microaneurysms in DME should be differentiated from the localized leaks of CSCR in such cases.
FIG. 10 A 62-year-old man presented with diminution of vision in both eyes for 1 year. He was diagnosed elsewhere with diabetic macular edema. (A) Fundus fluorescein angiography revealed multiple leaking microaneurysms (A). Optical coherence tomography showed macular edema, neurosensory detachment, double-layer sign along with a thick choroid (B). A diagnosis of central serous chorioretinopathy along with diabetic retinopathy was made.
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CONCLUSION CSCR presents with a plethora of changes that makes it one of the most commonly misdiagnosed conditions and also an object of a missed diagnosis. It is important to analyze the subtle changes that help in diagnosing or ruling out the disease. Various ancillary investigations often act as a useful adjunct to reach a definitive diagnosis.
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23. Yannuzzi L, Ciardella A, Spaide R, Rabb M, Freund K, Orlock D. The expanding clinical spectrum of idiopathic polypoidal choroidal vasculopathy (IPCV). In: Retinal Pigment Epithelium and Macular Diseases. Springer; 1998:173–183. 24. Moorthy RS, Lyon AT, Rabb MF, Spaide RF, Yannuzzi LA, Jampol LM. Idiopathic polypoidal choroidal vasculopathy of the macula. Ophthalmology. 1998;105(8):1380–1385. 25. Yannuzzi LA, Freund KB, Goldbaum M, et al. Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy. Ophthalmology. 2000;107(4):767–777. 26. Park HS, Kim IT. Clinical characteristics of polypoidal choroidal vasculopathy associated with chronic central serous chorioretionopathy. Korean J Ophthalmol. 2012;26(1):15–20. 27. Koizumi H, Yamagishi T, Yamazaki T, Kinoshita S. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol. 2013;155(2):305–313. e1. 28. Toyama T, Ohtomo K, Noda Y, Ueta T. Polypoidal choroidal vasculopathy and history of central serous chorioretinopathy. Eye. 2014;28(8):992–997. 29. Okushiba U, Takeda M. Study of choroidal vascular lesions in central serous chorioretinopathy using indocyanine green angiography. Nippon Ganka Gakkai Zasshi. 1997;101(1):74–82. 30. Spaide RF, Hall L, Haas A, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina (Philadelphia, PA). 1996;16(3):203–213. 31. Sasahara M, Tsujikawa A, Musashi K, et al. Polypoidal choroidal vasculopathy with choroidal vascular hyperpermeability. Am J Ophthalmol. 2006;142(4):601–607. e1. 32. Nakashizuka H, Mitsumata M, Okisaka S, et al. Clinicopathologic findings in polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2008;49(11):4729–4737. 33. Chung SE, Kang SW, Kim JH, Kim YT. Engorgement of vortex vein and polypoidal choroidal vasculopathy. Retina. 2013;33(4):834–840. 34. Yannuzzi LA, Negrao S, Iida T, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416–434. 35. Zaidi AA, Brucker AJ, Johnson MW. Diagnostic and therapeutic challenges. Retina. 2011;31(10):2125–2128. 36. Sugar HS. An explanation: for the acquired macular pathology associated with congenital pits of the optic disc. Am J Ophthalmol. 1964;57(5):833–835. 37. Gass JDM. Serous detachment of the macula: secondary to congenital pit of the optic nervehead. Am J Ophthalmol. 1969;67(6):821–841. 38. Wise GN, Dollery CT, Henkind P. The Retinal Circulation. Harpercollins; 1971. 39. Ferry AP. Macular detachment associated with congenital pit of the optic nerve head: pathologic findings in two cases simulating malignant melanoma of the choroid. Arch Ophthalmol. 1963;70(3):346–357. 40. Michalewski J, Michalewska Z, Nawrocki J. Spectral domain optical coherence tomography morphology in optic disc pit associated maculopathy. Indian J Ophthalmol. 2014;62(7):777–781. 41. Sobol WM, Blodi CF, Folk JC, Weingeist TA. Long-term visual outcome in patients with optic nerve pit and serous retinal detachment of the macula. Ophthalmology. 1990;97(11):1539–1542. 42. Snead M, James N, Jacobs P. Vitrectomy, argon laser, and gas tamponade for serous retinal detachment associated with an optic disc pit: a case report. Br J Ophthalmol. 1991;75(6):381–382. 43. Caillaux V, Gaucher D, Gualino V, Massin P, Tadayoni R, Gaudric A. Morphologic characterization of domeshaped macula in myopic eyes with serous macular detachment. Am J Ophthalmol. 2013;156(5):958–67. e1. 44. Imamura Y, Iida T, Maruko I, Zweifel SA, Spaide RF. Enhanced depth imaging optical coherence tomography of the sclera in dome-shaped macula. Am J Ophthalmol. 2011;151(2):297–302. 45. Deobhakta A, Ross AH, Helal J, Maia A, Freund KB. Localized choroidal thickness variation and pigment epithelial detachment in dome-shaped macula with subretinal fluid. Ophthalmic Surgery, Lasers and Imaging Retina. 2015;46(3):391–392. 46. Yzer S, Fung AT, Barbazetto I, Yannuzzi LA, Freund KB. Central serous chorioretinopathy in myopic patients. Arch Ophthalmol. 2012;130(10):1339–1340. 47. Manayath GJ, Arora S, Parikh H, Shah PK, Tiwari S, Narendran V. Is myopia a protective factor against central serous chorioretinopathy? Int J Ophthalmol. 2016;9(2):266. 48. Viola F, Dell’Arti L, Benatti E, et al. Choroidal findings in dome-shaped macula in highly myopic eyes: a longitudinal study. Am J Ophthalmol. 2015;159(1):44–52.
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49. Dirani A, Matet A, Beydoun T, Mantel I, Behar-Cohen F. Resolution of foveal detachment in dome-shaped macula after treatment by spironolactone: report of two cases and mini-review of the literature. Clin Ophthalmol. 2014;8:999–1002. 50. Gass JM, Gieser RG, Wilkinson CP, Beahm DE, Pautler SE. Bilateral diffuse uveal melanocytic proliferation in patients with occult carcinoma. Arch Ophthalmol. 1990;108(4):527–533. 51. Naysan J, Pang CE, Klein RW, Freund KB. Multimodal imaging of bilateral diffuse uveal melanocytic proliferation associated with an iris mass lesion. Int J Retina Vitreous. 2016;2:13. 52. Saito W, Kase S, Yoshida K, et al. Bilateral diffuse uveal melanocytic proliferation in a patient with cancer- associated retinopathy. Am J Ophthalmol. 2005;140(5):942–945. 53. Mashayekhi A, Shields CL. Circumscribed choroidal hemangioma. Curr Opin Ophthalmol. 2003;14(3):142–149. 54. Burgess R, Millar ID, Leroy BP, et al. Biallelic mutation of BEST1 causes a distinct retinopathy in humans. Am J Hum Genet. 2008;82(1):19–31. 55. Yardley J, Leroy BP, Hart-Holden N, et al. Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC). Invest Ophthalmol Vis Sci. 2004;45(10):3683–3689. 56. Boon CJ, Klevering BJ, Leroy BP, Hoyng CB, Keunen JE, den Hollander AI. The spectrum of ocular phenotypes caused by mutations in the BEST1 gene. Prog Retin Eye Res. 2009;28(3):187–205. 57. Ferrara DC, Costa RA, Tsang S, Calucci D, Jorge R, Freund KB. Multimodal fundus imaging in Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol. 2010;248(10):1377–1386. 58. Watzke RC, Packer AJ, Folk JC, Benson WE, Burgess D, Ober RR. Punctate inner choroidopathy. Am J Ophthalmol. 1984;98(5):572–584. 59. Birnbaum AD, Blair MP, Tessler HH, Goldstein DA. Subretinal fluid in acute posterior multifocal placoid pigment epitheliopathy. Retina (Philadelphia, PA). 2010;30(5):810. 60. Brodsky MC. Central serous papillopathy. Br J Ophthalmol. 1999;83(7):878. 61. Chao DL, Marsiglia M, Ahmad B, et al. Peripapillary serous detachment in multiple evanescent white dot syndrome. Retina. 2015;35(3):521–524. 62. Herbort CP, Mantovani A, Bouchenaki N. Indocyanine green angiography in Vogt–Koyanagi–Harada disease: angiographic signs and utility in patient follow-up. Int Ophthalmol. 2007;27(2–3):173–182. 63. Menchini U, Virgili G, Lanzetta P, Ferrari E. Indocyanine green angiography in central serous chorioretinopathy. Int Ophthalmol. 1997;21(2):57–69. 64. Dinc UA, Tatlipinar S, Yenerel M, Görgün E, Ciftci F. Fundus autofluorescence in acute and chronic central serous chorioretinopathy. Clin Exp Optom. 2011;94(5):452–457. 65. Roisman L, Lavinsky D, Magalhaes F, et al. Fundus autofluorescence and spectral domain OCT in central serous chorioretinopathy. J Ophthalmol. 2011;2011:. 66. Lin D, Chen W, Zhang G, et al. Comparison of the optical coherence tomographic characters between acute Vogt-Koyanagi-Harada disease and acute central serous chorioretinopathy. BMC Ophthalmol. 2014;14:87. 67. Papadia M, Jeannin B, Herbort CP. Central serous chorioretinopathy misdiagnosed as posterior uveitis and the vicious circle of corticosteroid therapy. J Ophthalmic Vis Res. 2015;10(3):303–308. 68. Franco M, Nogueira V. Severe acute syphilitic posterior placoid chorioretinitis with complete spontaneous resolution: the natural course. GMS Ophthalmol Cases. 2016;6:Doc02. 69. Rogers SL, McIntosh RL, Lim L, et al. Natural history of branch retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 2010;117(6):1094–101. e5. 70. Karia N. Retinal vein occlusion: pathophysiology and treatment options. Clin Ophthalmol. 2010;4:809. 71. Celık E, Doğan E, Turkoglu EB, Çakır B, Alagoz G. Serous retinal detachment in patients with macular edema secondary to branch retinal vein occlusion. Arq Bras Oftalmol. 2016;79(1):9–11. 72. Chang Y-S, Chang C, Weng S-F, Wang J-J, Jan R-L. Risk of retinal vein occlusion with central serous chorioretinopathy. Retina. 2016;36(4):798–804. 73. Gass JDM, Jallow S. Idiopathic serous detachment of the choroid, ciliary body, and retina (uveal effusion syndrome). Ophthalmology. 1982;89(9):1018–1032. 74. Uyama M, Takahashi K, Kozaki J, et al. Uveal effusion syndrome1: clinical features, surgical treatment, histologic examination of the sclera, and pathophysiology. Ophthalmology. 2000;107(3):441–449. 75. Gass J. Uveal effusion syndrome: a new hypothesis concerning pathogenesis and technique of surgical treatment. Trans Am Ophthalmol Soc. 1983;81:246. 76. Yannuzzi LA, Bardal AM, Freund KB, Chen K-J, Eandi CM, Blodi B. Idiopathic macular telangiectasia. Arch Ophthalmol. 2006;124(4):450–460.
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77. Gaudric A, de Lahitte GD, Cohen SY, Massin P, Haouchine B. Optical coherence tomography in group 2A idiopathic juxtafoveolar retinal telangiectasis. Arch Ophthalmol. 2006;124(10):1410–1419. 78. Mehta H, Müller S, Egan CA, et al. Natural history and effect of therapeutic interventions on subretinal fluid causing foveal detachment in macular telangiectasia type 2. Br J Ophthalmol. 2016;. bjophthalmol-2016-309237. 79. Matet A, Yzer S, Chew EY, Daruich A, Behar-Cohen F, Spaide RF. Concurrent idiopathic macular telangiectasia type 2 and central serous chorioretinopathy. Retina. 2018;38:S67–S78. 80. Watson PG. Clinical presentation of scleritis and episcleritis. In: Watson PG, Hazleman BL, Pavesio CE, Green WR, eds. The Sclera and Systemic Disorders. London: Butterworth-heinemann; 2004:60–88. 81. McCluskey PJ, Watson PG, Lightman S, Haybittle J, Restori M, Branley M. Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients. Ophthalmology. 1999;106(12):2380–2386. 82. Otani T, Kishi S, Maruyama Y. Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol. 1999;127(6):688–693. 83. Catier A, Tadayoni R, Paques M, et al. Characterization of macular edema from various etiologies by optical coherence tomography. Am J Ophthalmol. 2005;140(2):200. e1–e9. 84. Ozdemir H, Karacorlu M, Karacorlu S. Serous macular detachment in diabetic cystoid macular oedema. Acta Ophthalmol. 2005;83(1):63–66. 85. Kang SW, Park CY, Ham D-I. The correlation between fluorescein angiographic and optical coherence tomographic features in clinically significant diabetic macular edema. Am J Ophthalmol. 2004;137(2):313–322. 86. Nagaoka T, Kitaya N, Sugawara R, et al. Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes. Br J Ophthalmol. 2004;88(8):1060–1063. 87. Gaucher D, Sebah C, Erginay A, et al. Optical coherence tomography features during the evolution of serous retinal detachment in patients with diabetic macular edema. Am J Ophthalmol. 2008;145(2):289–296.e1.
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15 CSCR Masquerades Niroj Kumar Sahoo, Sumit Randhir Singh, Jay Chhablani Smt. Kanuri Santhamma Centre for Vitreo-Retinal Diseases, L.V. Prasad Eye Institute, Hyderabad, India
INTRODUCTION Central serous chorioretinopathy (CSCR) is primarily a disease of the choroid that typically affects middle-age men, manifesting as a neurosensory detachment of the posterior pole with or without an associated pigment epithelial detachment. Various risk factors implicated in the pathogenesis of the disease include corticosteroid exposure, phosphodiesterase inhibitor use, obstructive sleep apnea, and Type A personality traits. In its acute form, it can manifest with a wide range of visual disturbances such as central scotoma, metamorphopsia, dyschromatopsia, and micropsia,1, 2 which typically resolves within 3–4 months with or without treatment, leaving only disturbances in color vision in some patients.3 The chronic form, however, can be unforgiving for the patient, with the eye presenting with varying degrees of retinal pigment epithelium (RPE) abnormalities, often culminating in moderate to severe vision loss because of RPE atrophy in the central macula, foveal atrophy, or cystoid macular degeneration (CMD) involving the fovea.4–8 Rarely, certain atypical forms can present without the classic predisposing risk factors or might be unresponsive to conventional treatment. It is these myriad of posterior segment findings that often pose a diagnostic dilemma, considering the fact that a number of retinal and choroidal conditions can mimic such findings and masquerade CSCR. It is not uncommon to see a patient being diagnosed with CSCR and mismanaged until a correct diagnosis has been reached. Similarly, certain atypical presentations of CSCR have misdiagnosed as other retinal or choroidal pathologies. In this chapter, we intend to summarize some of these puzzling conditions that might lead the ophthalmologist toward a diagnosis of CSCR and the features that can aid in better differentiation. A summary of the various conditions is shown in Fig. 1.
CSCR AS INITIAL DIAGNOSIS These conditions usually present with neurosensory detachment of the posterior pole with ill-defined leaks similar to CSCR. A detailed ophthalmic evaluation with multimodal imaging often is needed to reach a correct diagnosis (Table 1).
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FIG. 1 Summary of an approach to a patient with subretinal fluid involving the macula.
Polypoidal Choroidal Vasculopathy (PCV)
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TABLE 1 Masquerades of Central Serous Chorioretinopathy (CSCR) CSCR as Initial Diagnosis
CSCR as Final Diagnosis
• Idiopathic choroidal neovascularization • Polypoidal choroidal vasculopathy • Retinal angiomatous proliferans • Cavitory optic disc anomalies including optic disc pit • Dome-shaped macula • Bilateral diffuse uveal melanocytic proliferation • Choroidal hemangioma • Bestrophinopathies • White dot syndrome
• Vogt-Koyanagi-Harada • Posterior uveitis • Tributary retinal vein occlusion • Uveal effusion syndrome • Idiopathic juxtafoveal telangiectasis • Posterior scleritis • Diabetic macular edema
IDIOPATHIC CHOROIDAL NEOVASCULARIZATION (CNV) Idiopathic CNV is primarily a disease of patients younger than 50 years and is characterized by development of CNV in the absence of pathologic myopia, angioid streaks, trauma, or any other inflammatory or hereditary disorders.9 It is most commonly a type 2 CNV.10 Lesions are usually small, well-defined, and extend above the RPE. Occasionally, it presents with a subretinal halo or pigmented plaque. Occasionally, the yellowish subretinal lesion in CNV can be confused with CSCR presenting with subretinal fibrin and vice versa. Dye angiography as a diagnostic tool often can be misleading, as idiopathic CNV also can present with an ink-blot type leak seen in CSCR. A CNV lesion should be suspected strongly in presence of subretinal lipid or hemorrhage, subretinal hyperreflective material, double-layer sign between RPE and Bruch’s membrane and interruptions in the RPE on optical coherence tomography (OCT).8, 11 Also, demonstration of the vascular network in idiopathic CNV by Fundus fluorescein angiography (FFA), Indocyanine green (ICG) or optical coherence tomography angiography (OCTA) often is diagnostic. Certain atypical type 2-like leaks have been demonstrated in CSCR, resulting from alteration in flow dynamics because of pigment epithelium detachment (PED) adherence to the retina.12 Finally, a CNV complex can be missed on OCT if the scan does not pass through the lesion. An illustrative case is shown in Fig. 2. CNV (especially type 1) arising in the setting of a chronic CSCR rarely can appear to be an idiopathic CNV on history and clinical examination as both the conditions can have pigment epithelial detachment, subretinal fluid, intraretinal fluid, cystoid macular degeneration, retinal atrophy, and diffuse irregular hyperfluorescence on angiogram.13 Careful examination of the OCT image is important in these cases, which reveal a thickened choroid in the former along with widespread RPE abnormalities. Idiopathic CNV usually responds to anti-VEGF (vascular endothelial growth factor) agents and has a better prognosis compared to neovascular age-related macular degeneration (AMD).14, 15 CNV secondary to CSCR, however, responds better with laser, photodynamic therapy (PDT), anti-VEGF agents, or a combination of the above.16–18
POLYPOIDAL CHOROIDAL VASCULOPATHY (PCV) PCV is a disease of the choroid and is believed to be a part of the pachychoroid spectrum of diseases. It typically affects older individuals in their fifth decade of life, and is characterized by reddish-orange, aneurysmal, or polypoidal lesion involving the posterior pole or
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FIG. 2 A 36-year-old man presented with diminution of vision in his right eye for 1 week. Fundus examination and optical coherence tomography showed neurosensory detachment of the macula (A, B) and inkblot leak pattern on fundus fluorescein angiography (C). A repeat scan through the leak site revealed the presence of a choroidal neovascular complex (D).
periphery. The classic presentation of a PCV lesion is a recurrent episode of exudative retinal detachment, subretinal hemorrhage, serous or hemorrhagic PED.19–21 However, it also can present with serous macular detachment associated with PED, which can give an impression of a CSCR.22–24 Similarly, neurosensory detachment along with subretinal or sub-RPE hemorrhage in a case of CNV secondary to CSCR can mimic a PCV lesion. Differentiating between these two entities becomes difficult in these circumstances because both conditions can present with a thickened choroid. A series of RPE changes seen in cases of CSCR often can mask an underlying PCV,22 and thus a PCV lesion always should be suspected in cases of nonresponding or persistent,25 and long standing CSCR.26 These lesions often are solitary and located at the margin or near the atrophic retina. The appearance of a PCV lesion in a case of CSCR often has led to the dilemma about whether these entities coexist in the same eye or whether CSCR, during the course of illness, transforms to PCV.26–28 In view to this observation, few studies have suggested a common pathogenesis of choroidal congestion and hyperpermeability for the two entities.29–31 Additionally, a PCV lesion has been described to be associated with arteriosclerotic changes32 and engorged vortex veins secondary to chronic choroidal venous congestion.33 ICG often is considered diagnostic in these lesions because it can delineate these polypoidal lesions (Fig. 3) and the branched vascular network in early phase associated with local pooling.
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FIG. 3 A 60-year old woman presented with diminution of vision in the right eye for 1 year. (A) Optical coherence tomography revealed a large neurosensory detachment involving the macula with a pigment epithelial detachment. (B) Fundus fluorescein angiography revealed multiple small polyps (arrowheads).
RETINAL ANGIOMATOSIS PROLIFERATION (RAP) RAP represents a distinct form of occult CNV that typically affects individuals in their eighth decade of life. It develops from the paramacular intraretinal capillaries and characterized by development of retinochoroidal anastomotic vessels. It was first described by Yannuzzi and co-workers as a variant of exudative AMD (Type 3). Three stages of development have been described: Stage 1: Intraretinal neovascularization with intraretinal edema and hemorrhage.34 Stage 2: Subretinal neovascularization because of extension of the neovascularization posteriorly, characterized by localized retinal detachment, intraretinal, preretinal hemorrhage, intraretinal edema, and serous PED.34 Stage 3: Choroidal neovascularization characterized by a fibrovascular PED and a retinochoroidal anastomosis..34 FFA has limited diagnostic role and the leak pattern seen in stage 2 lesion can sometimes closely resemble that of a CSCR. Features that suggest the presence of a RAP lesion are the older age of presentation, presence of blood in the intraretinal or subretinal space, and the pattern of leak in late phase of ICG angiography. ICG demonstrates focal areas on hyperfluorescence (hot spots), which increase in size as the dye diffuses into the intraretinal and subretinal space.34
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CAVITORY OPTIC DISC ANOMALIES INCLUDING OPTIC DISC PIT (ODP) ODP is a congenital anomaly of the optic disc characterized by focal excavation. Although it most commonly involves the inferotemporal aspect of the disc, any quadrant of the disc can be affected. It occurs because of a defect in the closure of the superior end of the embryonic fissure. Clinically, it manifests with varying degrees of field defects and often is seen to be complicated by a maculopathy. Macular involvement is in the form of serous retinal detachment and presence of multiple schitic cavities in the outer retina. The presence of these features, along with a central or occult/invisible pit, can portray a picture that is exactly the same as a CSCR lesion.35 The source of fluid in these cases is poorly understood. It is believed to be because of the passage of liquefied vitreous into the intraretinal and the subretinal space following traction by a posterior vitreous detachment.36 Other sources include CSF from the subarachnoid space,37 blood vessels at the ODP,37 choroidal vasculature through Bruch’s membrane, and the RPE.38 Absence of leak in FFA and the characteristic changes in the optic disc help to differentiate it from CSCR. Presence of schitic cavities, extent of the subretinal fluid up to the disc margins, and outer lamellar hole on OCT are some of the features that favor the diagnosis of optic disc pit, even when the pit is clinically subtle.35 OCT sometimes demonstrates focal excavation of dysplastic retina into a defect in the lamina cribrosa (Fig. 4).39 Hyporeflective areas also have
FIG. 4 A 23-year-old man presented with diminution of vision in the right eye for 1 year. (A) Optical coherence tomography (OCT) revealed a neurosensory detachment involving the macula. (B) Fundus image showed grayish discoloration on the temporal aspect of the disc (black arrow). (C) OCT scan through the optic nerve head revealed an optic disc pit with underlying hyporeflective areas (white arrow).
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been described below the areas of excavation.40 Unlike acute CSC, which it resembles, treatment of optic disc maculopathy is indicated in most cases because of poor natural history41 and it responds to pars plana vitrectomy (PPV) with laser and gas injection.42
DOME-SHAPED MACULA (DSM) DSM is described as a dome-shaped forward macular bulge seen in eyes with high myopia presenting with or without a posterior staphyloma. Around 50% of cases present with a neurosensory detachment involving the macula.43 A localized increased scleral thickness and an abrupt change in choroidal thickness has been suggested to be the underlying mechanism behind formation of SRF.44, 45 The clinical picture often closely resembles the CSCR lesion because of the similar leak patterns on FFA and ICG. Features specific to DSM, however, include high myopia, the forward bulge of the macula on OCT, the presence of choroidal thinning, and subfoveal choroidal thickening. (Fig. 5) Incidence of CSCR, on the other hand, is considered very low in these myopic eyes46 probably because of the significantly thin choroid.47 Most cases of DSM usually resolve spontaneously, however, persistent cases respond to PDT or aldosterone antagonist.48, 49
FIG. 5 A 43-year-old man presented with features of serous neurosensory detachment in the left eye (A) with inkblot-type of leak on fundus fluorescein angiography (B) and was being treated as central serous chorioretinopathy elsewhere. (C) Optical coherence tomography revealed a dome-shaped elevation at the macula.
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BILATERAL DIFFUSE UVEAL MELANOCYTIC PROLIFERATION (BDUMP) BDUMP is described classically as a paraneoplastic syndrome of the eye often seen in patients with occult, but advanced, visceral malignancies, most commonly ovarian, lung, gall bladder, cervical, uterine, kidney, pancreatic, breast, esophageal, and colorectal cancers. The main clinical features are multiple, faint, red, round, or oval patches at the level of the RPE (giraffe-pattern); multifocal areas of early hyperfluorescence corresponding with the patches on FFA; development of multiple, slightly elevated, pigmented, and nonpigmented uveal melanocytic tumors, with diffuse thickening of the uveal tract; exudative retinal detachment; and rapid progression of cataracts.50 Fundus autofluorescence (FAF) shows hyperautofluorescence corresponding to faint red lesions and hypoautofluorescence pattern corresponding to areas of RPE atrophy.51 A subretinal fluid and irregular and thickened RPE can be demonstrated on OCT.51 Visual prognosis usually is considered very poor and treatment options are limited to corticosteroid, external beam radiotherapy, surgery, and treatment of the visceral malignancy.50, 52
CHOROIDAL HEMANGIOMA Choroidal hemangiomas are benign vascular hamartomas that can be either diffuse or circumscribed. A circumscribed choroidal hemangioma classically presents as an orange-red lesion associated with serous macular detachment. Occasionally, however, it can mimic a CSCR, especially when it presents in a middle-age adult with a macular detachment that is large enough to obscure the choroidal lesion. Ancillary tests often are needed in such cases to reach at a definitive diagnosis. FAF imaging shows hypoautofluorescence corresponding to the area of the lesion. A lacy hyperfluorescence in choroidal phase can be demonstrated on FFA, which increases through the remaining phases of angiogram. ICG better delineates the intrinsic vacularity and demonstrates a phenomenon of wash out that is seen as a hypocyanescent or isocyanescent area with surrounding staining.53 The choroidal mass can be detected by ultrasonography, which shows acoustic solidity in B-scan and high internal reflectivity in A-scan (Fig. 6). Newer imaging modalities such as EDI-OCT often demonstrate an increased choroidal thickness in these lesions. Although an increased choroidal thickness also is seen in CSCR, it is often in the range of 500 μm,2 whereas the thickness is often more than 1000–2000 μm in choroidal hemangioma.
BESTROPHINOPATHIES Bestrophinopathies encompass a clinical spectrum of inherited macular dystrophies that are caused by mutation of the BEST 1 gene expressed in the RPE. It includes Best vitelliform macular dystrophy (BVMD), adult-onset vitelliform macular dystrophy (AVMD), autosomal dominant vitreoretinochoroidopathy (ADVIRC), and autosomal recessive bestrophinopathy (ARB).54, 55 A diminution of central vision and a neurosensory detachment
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FIG. 6 A 35-year-old woman presented with diminution of vision of left eye for 1 year. (A) Optical coherence tomography (OCT) revealed a neurosensory detachment. Careful fundus examination showed an orange-yellow elevated mass along the inferior arcade (B), which was confirmed by OCT (C). (D) Ultrasound B-scan imaging showed a mass in the posterior pole with acoustic solidity.
involving macula can be seen in all of these conditions. The subretinal deposits are seen on OCT as hyperreflective structures. This can simulate a CSCR presenting with subretinal fibrin. In certain cases, a clear subretinal fluid also can be present instead of these deposits, giving an impression of a CSCR. Also, the absence of the classical pseudohypopyon can further make the diagnosis more enigmatic. A ring of hyperautofluorescence can be seen in FAF in the areas of subretinal deposits as these are believed to be lipofuchsin precursors. Points in favor of bestrinopahthies, however, include a younger age group (although it can present as late as in the sixth decade in AVMD) and the characteristic clinical finding of bilateral, egg yolk-like round lesions affecting the macula..56 FFA demonstrates blocked fluorescence corresponding to the areas of subretinal deposits but also can show irregular hyperfluorescence. The diagnosis can be confirmed using EOG, which shows a decreased Arden’s ratio.57 A representative case is shown in Fig. 7. Examination of the family members, even when asymptomatic, can aid in the diagnosis without the need for the previously mentioned imaging modalities.
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(A)
(B)
(C) µV 1500
Minimum = 266 µV
1000
Maximum = 297 µV
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Arden ratio = 112 %
0
0
(D)
5
10
15
20
25
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FIG. 7 A 35-year-old woman presented with history of diminution of vision in both eyes for 2 years. (A, B) Optical coherence tomography and fundus imaging revealed a neurosensory detachment. (C) Fundus autofluorescence showed punctate hyperautofluorescent spots at the margin of the lesion. (D) Electro-oculogram confirmed the diagnosis of Best disease that showed a decreased Arden ratio.
WHITE DOT SYNDROME (WDS) WDS is a heterogeneous group of multifocal inflammatory conditions characterized by multiple white-yellow lesions involving the outer retina, RPE, or choroid. It often is accompanied by a hyperpermeable choroid, which is responsible for its exudative manifestations. Serous macular detachment has been described with punctate inner choroidopathy (PIC) and acute posterior multifocal placoid pigment epitheliopathy (APMPPE).58, 59 Features that help in differentiating it from certain atypical forms of CSCR60 are the typical whitish-yellow lesions in the posterior pole and FFA showing early hypofluorescence
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Posterior Uveitis
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and late hyperfluorescence. Serous retinal detachment also has been described in cases of MEWDS.61 Finally, certain WDS-like serpiginous choroiditis, multifocal choroiditis and panuveitis (MCP), PIC, progressive subretinal fibrosis and uveitis (SFU), and multiple evanescent white dot syndrome (MEWDS) also have been described as being complicated by a CNVM that can mimic a CSCR. Angiogram is helpful in these cases to help delineate the neovascular membrane.
CSCR AS FINAL DIAGNOSIS Considering the wide range of manifestations seen with CSCR, especially the atypical forms, it is not uncommon to find a misdiagnosed and mismanaged case of CSCR. This often leads to exacerbation of the disease. Nonresponse to treatment or aggravation of signs should point toward a diagnosis of CSCR. Some of these conditions are described in Table 1.
VOGT-KOYANAGI-HARADA (VKH) VKH is a bilateral granulomatous panuveitis affecting young individuals, characterized by a diffuse choroidal inflammation with or without extraocular manifestations. It is one of the most common conditions that CSCR is misdiagnosed as, because both the conditions can present with thickened choroid, exudative retinal detachment, and pinpoint leaks on FFA (atypical CSCR). Because VKH is an inflammatory condition, it is marked by anterior chamber and vitreous cells and optic disc edema. These findings, however, are not seen in CSCR, because it is a disease of the intrinsic choroidal vascularity. Careful examination of various imaging modalities can reveal certain subtle signs that can help in differentiating between the two conditions. The pinpoint leak seen in VKH usually is associated with late prominent pooling in the area of SRF along with disc leak, while it is less leaky in CSCR. A diffuse choroidal hyperpermeability, hypofluorescent dark dots, and optic disc staining are characteristic of VKH on ICG,62 while the choroidal hyperpermeability usually is localized in CSCR.63 Also, speckled hyperautofluorescence corresponding to the leak points on FAF is a feature specific to CSCR.64, 65 The classic finding of increased RPE undulation index, RPE folds, fluctuation of ILM, and subretinal septa also have been described only with VKH, whereas, RPE hyperplasia and PED is seen more commonly with CSCR.66 An illustrative case is demonstrated in Fig. 8. On ultrasonography, a low to medium reflective choroidal thickening in the posterior fundus is typical for VKH. It is important to distinguish between the two entities because corticosteroids used in the treatment of VKH can lead to a worsening or lack of response in a case of CSCR.
POSTERIOR UVEITIS Posterior uveitis is a group of disorders having diffuse choroidal inflammation as a common underlying pathology. The incidence of CSCR seen in patients diagnosed with posterior uveitis is high, because of both misdiagnosis and use of steroids. Misdiagnosis of CSCR for posterior uveitis can lead to intensification of steroids, which can be devastating for CSCR.
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FIG. 8 A 44-year-old man presented with diminution of vision in both eyes for 1 month. Optical coherence tomography showed neurosensory detachment of the posterior pole with retinal pigment epithelium undulations (A). Multiple pockets of pooling and pinpoint hyperfluorescence were seen in fundus fluorescein angiography (B). A diagnosis of Vogt Koyanagi Harada syndrome was made.
Atypical CSCR presenting with yellowish subretinal fibrin, bullous exudative retinal detachment, and multifocal leaks on angiogram can closely resemble a choroiditis lesion. It is important to rule out signs of inflammation of posterior segment on biomicroscopy, FFA (disk leak, retinal vasculitis), or ICG (choroiditis or dark dots). Thus, a patient presenting with exudative retinal detachment, minimal signs of ocular inflammation, and nonresponse to steroids suggests a diagnosis of steroid-induced CSCR. Also, the presence of classical signs of diffuse exudative epitheliopathy, localized leak patterns, hyperpermeable choroidal vessels, and bilaterality, are more in favor of a CSCR.67 A placoid fundus lesion with subretinal fluid seen in ocular syphilis easily can mimic chronic CSCR with fibrin. These patients show prompt response to injections of penicillin.68
TRIBUTARY RETINAL VEIN OCCLUSION (TRVO) Retinal vein occlusion (RVO) is the second-most common vascular disease after diabetic retinopathy.69 The usual manifestation is a cystoid macular edema (CME) that results because
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of increase in vascular permeability. This is believed to be secondary to an increase in intravascular pressure resulting in dysfunction of the endothelial blood-retinal barrier.70 Although rare, the appearance of a neurosensory detachment has been proposed to be a result of traction on the muller cell cone by the expanding CME that breaks the ELM barrier.71 Signs that suggest a diagnosis of TRVO in a patient with SRD include flame-shaped retinal hemorrhages, cotton wool spots, and an occluded/sclerosed tributary retinal vein. Neovascularization and collaterals also can be seen in long-standing cases. FFA acts as a useful adjunct in the diagnosis because it helps to delineate the capillary nonperfusion areas and macular involvement in these patients. A relationship between risk of RVO and presence of CSCR also has been proposed.72
UVEAL EFFUSION SYNDROME (UES) Uveal effusion syndrome is a rare, ocular disorder that typically affects middle-age men, and is characterized by idiopathic serous detachment of choroid, ciliary body, and retina.73 The pathogenetic mechanism behind the development of the uveal effusion syndrome is believed to be a thickened sclera resulting from the accumulation of glycosaminoglycans.74 This decreases the trans-scleral movement of protein, which, in turn, results in accumulation of protein in the extravascular space. This change in the concentration gradient prevents the movement of fluid from the suprachoroidal space to the choroidal circulation, and a choroidal effusion ensues.52 Compression of the vortex veins and the resultant choriocapillary congestion is suggested to be another mechanism.75 The mechanism behind the formation of a retinal detachment is believed to be a decompensated RPE because of long-standing choroidal detachment. This can mimic a bullous variant of CSCR. A choroidal detachment observed both opthalmoscopically and on ultrasonography, however, clinches the diagnosis of UES. In addition, ICG shows diffuse granular choroidal hyperfluorescence in the early phase and classical leopard spots, which is in contrast to the focal leaks of CSCR.74 Nanophthalmos should be ruled out in these cases, which can manifest with a similar scleropathy.74
IDIOPATHIC JUXTAFOVEOLAR RETINAL TELANGIECTASIS (IJFT) IJFT refers to a heterogenous group of clinical conditions that is characterized by telangiectactic alteration of the juxtfoveal capillary network. It manifests as incompetence, ectasia, or irregular dilations of the capillaries in the juxtafoveolar region. Two distinct types have been described. MacTel type 1 is congenital and unilateral variant that presents with aneurysmal dilatation of the juxtafoveal capillaries. MacTel type 2 (most common) is an acquired, bilateral variant.76 Typical ophthalmoscopic findings include a right-angled vessel associated with pigmentation and a foveal atrophy on OCT. The appearance of subretinal neovascularization (SRNV) often is accompanied by a neurosensory detachment of the macula. This detachment, however, can occur even without the presence of a SRNV and can resemble a CSCR, because the telangiectactic vessels can be subtle/occult in certain cases of MacTel type 2.77, 78 Demonstration of these SRNVs and telangiectatic vessels on angiography usually makes the diagnosis clear. Coexisting CSCR and IJFT also have been described.79
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POSTERIOR SCLERITIS Posterior scleritis, a painful inflammatory condition of the posterior sclera, typically is seen in middle-age women, although any age group can be affected. It can be either idiopathic or associated with other conditions such as herpes zoster ophthalmic, herpes simplex, syphilis, tuberculosis, rheumatoid arthritis, systemic lupus erythematosus, Wegener’s granulomatosis, polyarteritis nodosa, giant cell arteritis, ulcerative colitis, and Crohn’s disease.80, 81 Fundus usually shows choroidal folds, optic disk edema, serous retinal detachment and choroidal detachment. The degree of vision impairment depend upon the severity of macular involvement. Apart from the presence of a serous retinal detachment, several similarities exist between posterior scleritis and CSCR. These similarities include multiple pinpoint leaks on FFA and increased choroidal thickness on OCT. The presence of external manifestations such as hyperemia, proptosis, and painful eye movements (because of muscle involvement), however, rules out CSCR. Although not pathognomonic, demonstration of a T-sign on ultrasonography, which represents fluid collection in the sub-tenon’s space and the optic nerve sheath, with variable degree of thickening of choroid and sclera, favors the diagnosis of posterior scleritis (Fig. 9).
FIG. 9 A 27-year-old woman presented with diminution of vision in the right eye along with mild pain and redness. Optical coherence tomography revealed a bulge in the posterior pole (A). On ultrasound B-scan, fluid in the subtenon’s space and optic nerve sheath was seen (B).
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DIABETIC MACULAR EDEMA Although uncommon, serous retinal detachment in DME has been reported in about 15%– 30% of eyes.82–84 The source of the fluid is believed to be a hyperpermeable retinal vasculature85 or the choroidal circulation.86 The presence of serous retinal detachment, however, is not related to the retinal thickness or the stage of DME.83, 87 It is important to look for the presence of features suggestive of diabetic retinopathy, such as microanuerysms, neovascularisation, and leakage from the retinal vasculature, which can be differentiated easily from the focal leaks at the level of RPE in CSCR on FFA. Presence of shallow subretinal fluid and a thickened choroid should raise the suspicion of CSCR (Fig. 10). It is not uncommon, however, to see both the conditions coexisting in the same patient. Leaks from microaneurysms in DME should be differentiated from the localized leaks of CSCR in such cases.
FIG. 10 A 62-year-old man presented with diminution of vision in both eyes for 1 year. He was diagnosed elsewhere with diabetic macular edema. (A) Fundus fluorescein angiography revealed multiple leaking microaneurysms (A). Optical coherence tomography showed macular edema, neurosensory detachment, double-layer sign along with a thick choroid (B). A diagnosis of central serous chorioretinopathy along with diabetic retinopathy was made.
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CONCLUSION CSCR presents with a plethora of changes that makes it one of the most commonly misdiagnosed conditions and also an object of a missed diagnosis. It is important to analyze the subtle changes that help in diagnosing or ruling out the disease. Various ancillary investigations often act as a useful adjunct to reach a definitive diagnosis.
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