FOCAL RETINAL PIGMENT EPITHELIUM BREAKS IN CENTRAL SEROUS CHORIORETINOPATHY Michael D. Ober, MD,*† Chiara M. Eandi, MD,†‡ Lee M. Jampol, MD,§ Howard F. Fine, MD, MHSC,† Lawrence A. Yannuzzi, MD†
Purpose: To describe new evidence supporting a theory on the etiology of the focal retinal pigment epithelium (RPE) leak in central serous chorioretinopathy (CSC). Methods: The records of two patients with CSC were reviewed, including examination details and results of fluorescein angiography, fundus autofluorescence imaging, and optical coherence tomography (OCT). Results: A defect in the RPE monolayer demonstrated with OCT that corresponded to the site of the focal leak shown by fluorescein angiography was found in both patients. Conclusion: The focal leak shown by fluorescein angiography in patients with active CSC is caused by an RPE defect in at least some cases. This finding supports a previously reported theory on the pathogenesis of CSC. RETINAL CASES & BRIEF REPORTS 1:271–273, 2007
From the *Department of Ophthalmology, Henry Ford Health Systems, Detroit, Michigan; †The LuEsther T. Mertz Retina Research Center of Manhattan Eye, Ear, and Throat Hospital, and Vitreous–Retina– Macula Consultants of New York, New York, New York; the ‡Department of Clinic Physiopathology, Eye Clinic, University of Torino, Torino, Italy; and the §Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
which fluid enters the subretinal space, however, is controversial. Surely in chronic disease, with widespread decompensation of the pigment epithelium, there is diffusion or incontinence of the RPE resulting in fluid movement from the choroid to the subretinal space and chronic elevation of the neurosensory retina.1 In the acute stage of the disease, it has been postulated that inner choroidal accumulation of exudation predisposing to serous pigment epithelial detachments (PEDs) may result in a “blowout” or micro–pigment epithelial rip, usually at or near the margin of a PED. This results in a focal RPE leak, evident with FA, and detachment of the neurosensory retina.2–5 This concept is attractive and rationale but still unproven. We describe two patients who had acute CSC with a focal RPE leak and optical coherence tomography (OCT) and fundus autofluorescence imaging evidence to support this hypothesis.
I
n spite of being recognized as a distinct clinical entity for ⬎1 century, there is still a prevailing and perplexing uncertainty regarding the pathogenesis of central serous chorioretinopathy (CSC).1–3 With the advent of fluorescein angiography (FA), a focal leak at the level of the retinal pigment epithelium (RPE), resulting in a neurosensory detachment, has been the defining feature of the disease. The mechanism in The authors have no financial interests in any aspect of this study. Supported by the Macula Foundation, Inc. (New York, NY), and in part by an unrestricted grant from Research to Prevent Blindness, Inc. (New York, NY), to Northwestern University. Reprint requests: Lawrence A. Yannuzzi, MD, LuEsther T. Mertz Retinal Research Center of Manhattan Eye, Ear, and Throat Hospital, 210 East 64th Street, New York, NY 10021; e-mail: [email protected]
Case Reports Case 1 A 44-year-old man presented with a history of CSC and visual disturbances in his right eye for 1 year. He had been treated with thermal laser photocoagulation in the right eye 4 months earlier
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Fig. 1. A, Early-phase fluorescein angiography (FA) shows a focal leak (arrow) at the level of the retinal pigment epithelium (RPE) in the central macula. B, Corresponding latephase FA shows increased leakage (arrow). C, Fundus autofluorescence imaging shows the location of the hypoautofluorescent focal leak (arrow). The additional hypoautofluorescent spots represent areas of RPE atrophy and are seen as window defects by FA (A and B). D, Horizontal optical coherence tomography (orientation shown as red line in B) through the focal leak demonstrates the RPE disruption (short arrow) within a RPE detachment (arrowhead). Subretinal exudate is visible between the neurosensory detachment and the RPE layer (long arrow).
when best-corrected visual acuity was 20/100 in the right eye and 20/20 in the left eye. Fundus biomicroscopy showed mild pigment epithelial disturbances with a shallow neurosensory retinal detachment in the central macula of the right eye and an acute neurosensory retinal detachment inferiorly in the left eye. FA of the right eye revealed a focal leak in the central macula (Fig. 1, A and B), located within a zone of choroidal hyperpermeability shown by indocyanine green angiography. OCT demonstrated the presence of the retinal detachment with accumulation of exudative material (possibly fibrin) between the neurosensory retina and the pigment epithelium layer. Moreover, OCT showed a focal disruption of the RPE monolayer localized to the site of the focal leak demonstrated by FA (Fig. 1D). Fundus autofluorescence imaging demonstrated hypoautofluorescence corresponding precisely to the location of this defect (Fig. 1C).
Case 2 A 52-year-old man presented with the diagnosis of chronic CSC and recent visual loss in his right eye for 2 weeks. Best-corrected visual acuity was 20/200 in the right eye and 20/25 in the left eye. Biomicroscopic examination revealed multiple RPE detachments involving the macula of the right eye. A focal leak into the subretinal space was evident by FA at the edge of an RPE detachment (Fig. 2, A and B). The red-free and autofluorescence images revealed a stalk of scrolled RPE within the area of focal leakage demonstrating the torn edges. OCT confirmed this focal RPE disruption within an RPE detachment corresponding to the site of the leak demonstrated by FA (Fig. 2D). This same area exhibited hypoautofluorescence (Fig. 2C).
Discussion FA is the existing standard for defining acute CSC by the focal RPE leak leading to a detachment of the
neurosensory retina. OCT has enhanced our ability to identify and monitor certain clinical manifestations in CSC.6 For example, the localization of a very shallow or so-called “occult” neurosensory retinal detachment, a small PED, and even cystic degeneration of thefovea can be established with this imaging technique.7 Recognition of these subtle changes is useful in monitoring and managing the clinical course and establishing a visual prognosis. In addition, fundus autofluorescence imaging has recently been used to distinguish atrophic from degenerative RPE and to identify degenerating RPE and photoreceptors, neurosensory detachments, and even the location of an acute RPE leak.8,9 Whereas small molecules can pass through the RPE when it is degenerative from chronic detachment, larger molecules such as fibrin or its precursor fibrinogen are not likely to penetrate that barrier. Diffuse decompensation of the RPE leads to indistinct fluorescein leakage or a gradual so-called “ooze.” In these two cases of acute CSC, combined OCT and fundus autofluorescence imaging localized a serous PED and specifically identified the focal RPE leak evident by FA as a discrete disruption in the RPE continuity (blowout or micro–pigment epithelial rip). The fluorescein leak was pinpoint or focal, and it corresponded to the defect in the RPE at the margin of the PED. In our cases, fibrin was also identified under the neurosensory retina at clinical examination and confirmed with OCT.
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Fig. 2. A, Early-phase fluorescein angiography (FA) shows focal hyperfluorescence (arrow) within a larger retinal pigment epithelium (RPE) detachment. B, Corresponding late-phase FA shows descending fluorescein leakage emanating from the focal RPE disruption (arrow). C, Autofluorescence imaging shows an area of focal hyperautofluorescence (arrow) corresponding to a scrolled edge of RPE surrounded by a zone of hypoautofluorescence corresponding to the absence of RPE. D, Horizontal optical coherence tomography through the focal fluorescein leak (orientation shown as red line in A) demonstrates a disruption in the RPE (arrow) within an RPE detachment (arrowheads).
These two cases support the concept that a mechanical disruption in the PED may provide fluid, including large molecules such as fibrin, access to the subretinal space, resulting in a focal leak shown with FA in the acute stage of the disease. In fact, we believe that the sequence of events starts in the early stages of acute CSC with an increase in hydrostatic pressure within the inner choroid secondary to choroidal vascular hyperpermeability, as seen by indocyanine green angiography.3,10 This leads to serous PED as the fluid passes through Bruch membrane to elevate the loosely adherent pigment epithelium. The RPE disrupts somewhere near the junction of attached and detached pigment epithelium, allowing fluid to pass from the choroid to the subretinal space yielding the characteristic neurosensory detachment. A blowout or microrip of the RPE has been suggested as generating the focal FA leak but to our knowledge has never been previously demonstrated.2,5,11 This leak overwhelms the RPE transport of fluid from the subretinal space to the choroid. The presence of large subretinal exudative particles that originate from the choroid can be explained on the basis of a mechanical defect or opening in the RPE. Given the FA, OCT, and fundus autofluorescence images precisely registered in our cases, acute CSC can now definitely be attributed to a blowout or microrip, which was first suggested by Goldstein and Pavan,5 at least in some cases. This appears to occur when stress from choroidal hydrostatic pressure and mechanical stretching from the elevated RPE overcome intercellular adhesion forces. These cases serve to enhance our knowledge of the pathogenesis of CSC, at least in the acute stage of the
disease, and hopefully this knowledge will eventually lead to a better approach to therapy.
References 1. 2.
3.
4.
5. 6.
7.
8.
9.
10.
11.
Yannuzzi LA. Type-A behavior and central serous chorioretinopathy. Retina 1987;7:111–131. Spaide RF, Campeas L, Haas A, et al. Central serous chorioretinopathy in younger and older adults. Ophthalmology 1996;103:2070–2079. Guyer DR, Yannuzzi LA, Slakter JS, et al. Digital indocyanine green videoangiography of central serous chorioretinopathy. Arch Ophthalmol 1994;112:1057–1062. Cardillo Piccolino F, Borgia L. Central serous chorioretinopathy and indocyanine green angiography. Retina 1994;14: 231–242. Goldstein BG, Pavan PR. ‘Blow-outs’ in the retinal pigment epithelium. Br J Ophthalmol 1987;71:676–681. Hee MR, Puliafito CA, Wong C, et al. Optical coherence tomography of central serous chorioretinopathy. Am J Ophthalmol 1995;120:65–74. Iida T, Yannuzzi LA, Spaide RF, et al. Cystoid macular degeneration in chronic central serous chorioretinopathy. Retina 2003;23:1–7. Eandi CM, Ober MD, Iranmanesh R, et al. Acute central serous chorioretinopathy and fundus autofluorescence. Retina 2005;25:989–993. Spaide RF, Klancnik JM Jr. Fundus autofluorescence and central serous chorioretinopathy. Ophthalmology 2005;112: 825–833. Spaide RF, Hall L, Hass A, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina 1996;16:203–213. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology 2002;109:1834–1837.
Purpose: To describe new evidence supporting a theory on the etiology of the focal retinal pigment epithelium (RPE) leak in central serous chorioretinopathy (CSC). Methods: The records of two patients with CSC were reviewed, including examination details and results of fluorescein angiography, fundus autofluorescence imaging, and optical coherence tomography (OCT). Results: A defect in the RPE monolayer demonstrated with OCT that corresponded to the site of the focal leak shown by fluorescein angiography was found in both patients. Conclusion: The focal leak shown by fluorescein angiography in patients with active CSC is caused by an RPE defect in at least some cases. This finding supports a previously reported theory on the pathogenesis of CSC. RETINAL CASES & BRIEF REPORTS 1:271–273, 2007
From the *Department of Ophthalmology, Henry Ford Health Systems, Detroit, Michigan; †The LuEsther T. Mertz Retina Research Center of Manhattan Eye, Ear, and Throat Hospital, and Vitreous–Retina– Macula Consultants of New York, New York, New York; the ‡Department of Clinic Physiopathology, Eye Clinic, University of Torino, Torino, Italy; and the §Department of Ophthalmology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois.
which fluid enters the subretinal space, however, is controversial. Surely in chronic disease, with widespread decompensation of the pigment epithelium, there is diffusion or incontinence of the RPE resulting in fluid movement from the choroid to the subretinal space and chronic elevation of the neurosensory retina.1 In the acute stage of the disease, it has been postulated that inner choroidal accumulation of exudation predisposing to serous pigment epithelial detachments (PEDs) may result in a “blowout” or micro–pigment epithelial rip, usually at or near the margin of a PED. This results in a focal RPE leak, evident with FA, and detachment of the neurosensory retina.2–5 This concept is attractive and rationale but still unproven. We describe two patients who had acute CSC with a focal RPE leak and optical coherence tomography (OCT) and fundus autofluorescence imaging evidence to support this hypothesis.
I
n spite of being recognized as a distinct clinical entity for ⬎1 century, there is still a prevailing and perplexing uncertainty regarding the pathogenesis of central serous chorioretinopathy (CSC).1–3 With the advent of fluorescein angiography (FA), a focal leak at the level of the retinal pigment epithelium (RPE), resulting in a neurosensory detachment, has been the defining feature of the disease. The mechanism in The authors have no financial interests in any aspect of this study. Supported by the Macula Foundation, Inc. (New York, NY), and in part by an unrestricted grant from Research to Prevent Blindness, Inc. (New York, NY), to Northwestern University. Reprint requests: Lawrence A. Yannuzzi, MD, LuEsther T. Mertz Retinal Research Center of Manhattan Eye, Ear, and Throat Hospital, 210 East 64th Street, New York, NY 10021; e-mail: [email protected]
Case Reports Case 1 A 44-year-old man presented with a history of CSC and visual disturbances in his right eye for 1 year. He had been treated with thermal laser photocoagulation in the right eye 4 months earlier
271
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Fig. 1. A, Early-phase fluorescein angiography (FA) shows a focal leak (arrow) at the level of the retinal pigment epithelium (RPE) in the central macula. B, Corresponding latephase FA shows increased leakage (arrow). C, Fundus autofluorescence imaging shows the location of the hypoautofluorescent focal leak (arrow). The additional hypoautofluorescent spots represent areas of RPE atrophy and are seen as window defects by FA (A and B). D, Horizontal optical coherence tomography (orientation shown as red line in B) through the focal leak demonstrates the RPE disruption (short arrow) within a RPE detachment (arrowhead). Subretinal exudate is visible between the neurosensory detachment and the RPE layer (long arrow).
when best-corrected visual acuity was 20/100 in the right eye and 20/20 in the left eye. Fundus biomicroscopy showed mild pigment epithelial disturbances with a shallow neurosensory retinal detachment in the central macula of the right eye and an acute neurosensory retinal detachment inferiorly in the left eye. FA of the right eye revealed a focal leak in the central macula (Fig. 1, A and B), located within a zone of choroidal hyperpermeability shown by indocyanine green angiography. OCT demonstrated the presence of the retinal detachment with accumulation of exudative material (possibly fibrin) between the neurosensory retina and the pigment epithelium layer. Moreover, OCT showed a focal disruption of the RPE monolayer localized to the site of the focal leak demonstrated by FA (Fig. 1D). Fundus autofluorescence imaging demonstrated hypoautofluorescence corresponding precisely to the location of this defect (Fig. 1C).
Case 2 A 52-year-old man presented with the diagnosis of chronic CSC and recent visual loss in his right eye for 2 weeks. Best-corrected visual acuity was 20/200 in the right eye and 20/25 in the left eye. Biomicroscopic examination revealed multiple RPE detachments involving the macula of the right eye. A focal leak into the subretinal space was evident by FA at the edge of an RPE detachment (Fig. 2, A and B). The red-free and autofluorescence images revealed a stalk of scrolled RPE within the area of focal leakage demonstrating the torn edges. OCT confirmed this focal RPE disruption within an RPE detachment corresponding to the site of the leak demonstrated by FA (Fig. 2D). This same area exhibited hypoautofluorescence (Fig. 2C).
Discussion FA is the existing standard for defining acute CSC by the focal RPE leak leading to a detachment of the
neurosensory retina. OCT has enhanced our ability to identify and monitor certain clinical manifestations in CSC.6 For example, the localization of a very shallow or so-called “occult” neurosensory retinal detachment, a small PED, and even cystic degeneration of thefovea can be established with this imaging technique.7 Recognition of these subtle changes is useful in monitoring and managing the clinical course and establishing a visual prognosis. In addition, fundus autofluorescence imaging has recently been used to distinguish atrophic from degenerative RPE and to identify degenerating RPE and photoreceptors, neurosensory detachments, and even the location of an acute RPE leak.8,9 Whereas small molecules can pass through the RPE when it is degenerative from chronic detachment, larger molecules such as fibrin or its precursor fibrinogen are not likely to penetrate that barrier. Diffuse decompensation of the RPE leads to indistinct fluorescein leakage or a gradual so-called “ooze.” In these two cases of acute CSC, combined OCT and fundus autofluorescence imaging localized a serous PED and specifically identified the focal RPE leak evident by FA as a discrete disruption in the RPE continuity (blowout or micro–pigment epithelial rip). The fluorescein leak was pinpoint or focal, and it corresponded to the defect in the RPE at the margin of the PED. In our cases, fibrin was also identified under the neurosensory retina at clinical examination and confirmed with OCT.
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Fig. 2. A, Early-phase fluorescein angiography (FA) shows focal hyperfluorescence (arrow) within a larger retinal pigment epithelium (RPE) detachment. B, Corresponding late-phase FA shows descending fluorescein leakage emanating from the focal RPE disruption (arrow). C, Autofluorescence imaging shows an area of focal hyperautofluorescence (arrow) corresponding to a scrolled edge of RPE surrounded by a zone of hypoautofluorescence corresponding to the absence of RPE. D, Horizontal optical coherence tomography through the focal fluorescein leak (orientation shown as red line in A) demonstrates a disruption in the RPE (arrow) within an RPE detachment (arrowheads).
These two cases support the concept that a mechanical disruption in the PED may provide fluid, including large molecules such as fibrin, access to the subretinal space, resulting in a focal leak shown with FA in the acute stage of the disease. In fact, we believe that the sequence of events starts in the early stages of acute CSC with an increase in hydrostatic pressure within the inner choroid secondary to choroidal vascular hyperpermeability, as seen by indocyanine green angiography.3,10 This leads to serous PED as the fluid passes through Bruch membrane to elevate the loosely adherent pigment epithelium. The RPE disrupts somewhere near the junction of attached and detached pigment epithelium, allowing fluid to pass from the choroid to the subretinal space yielding the characteristic neurosensory detachment. A blowout or microrip of the RPE has been suggested as generating the focal FA leak but to our knowledge has never been previously demonstrated.2,5,11 This leak overwhelms the RPE transport of fluid from the subretinal space to the choroid. The presence of large subretinal exudative particles that originate from the choroid can be explained on the basis of a mechanical defect or opening in the RPE. Given the FA, OCT, and fundus autofluorescence images precisely registered in our cases, acute CSC can now definitely be attributed to a blowout or microrip, which was first suggested by Goldstein and Pavan,5 at least in some cases. This appears to occur when stress from choroidal hydrostatic pressure and mechanical stretching from the elevated RPE overcome intercellular adhesion forces. These cases serve to enhance our knowledge of the pathogenesis of CSC, at least in the acute stage of the
disease, and hopefully this knowledge will eventually lead to a better approach to therapy.
References 1. 2.
3.
4.
5. 6.
7.
8.
9.
10.
11.
Yannuzzi LA. Type-A behavior and central serous chorioretinopathy. Retina 1987;7:111–131. Spaide RF, Campeas L, Haas A, et al. Central serous chorioretinopathy in younger and older adults. Ophthalmology 1996;103:2070–2079. Guyer DR, Yannuzzi LA, Slakter JS, et al. Digital indocyanine green videoangiography of central serous chorioretinopathy. Arch Ophthalmol 1994;112:1057–1062. Cardillo Piccolino F, Borgia L. Central serous chorioretinopathy and indocyanine green angiography. Retina 1994;14: 231–242. Goldstein BG, Pavan PR. ‘Blow-outs’ in the retinal pigment epithelium. Br J Ophthalmol 1987;71:676–681. Hee MR, Puliafito CA, Wong C, et al. Optical coherence tomography of central serous chorioretinopathy. Am J Ophthalmol 1995;120:65–74. Iida T, Yannuzzi LA, Spaide RF, et al. Cystoid macular degeneration in chronic central serous chorioretinopathy. Retina 2003;23:1–7. Eandi CM, Ober MD, Iranmanesh R, et al. Acute central serous chorioretinopathy and fundus autofluorescence. Retina 2005;25:989–993. Spaide RF, Klancnik JM Jr. Fundus autofluorescence and central serous chorioretinopathy. Ophthalmology 2005;112: 825–833. Spaide RF, Hall L, Hass A, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina 1996;16:203–213. Carvalho-Recchia CA, Yannuzzi LA, Negrao S, et al. Corticosteroids and central serous chorioretinopathy. Ophthalmology 2002;109:1834–1837.
