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Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy
Polypoidal Choroidal Vasculopathy Masquerading as Central Serous Chorioretinopathy Lawrence A. Yannuzzi, MD, K. Bailey Freund, MD, Mauro Goldbaum, MD, Baldo Scassellati-Sforzolini, MD, David R. Guyer, MD, Richard F. Spaide, MD, David Maberley, MD, Doric W. K. Wong, MD, Jason S. Slakter, MD, John A. Sorenson, MD, Yale L. Fisher, MD, Dennis A. Orlock, CRA Objective: To differentiate polypoidal choroidal vasculopathy (PCV) from central serous chorioretinopathy (CSC). Design: A retrospective, observational case series. Participants: Thirteen patients originally diagnosed with CSC proved to have PCV after more extensive evaluation and follow-up. Methods: A clinical and angiographic review of patients with manifestations of CSC, including macular detachment. Main Outcome Measures: Demographic data, funduscopic examination, and fluorescein and indocyanine green (ICG) angiographic findings. Results: Thirteen patients initially suspected of having CSC were ultimately diagnosed as having PCV. These eyes had exudative macular detachments secondary to a small caliber, polypoidal choroidal vascular abnormality or so-called polypoidal choroidal neovascularization. The clinical manifestations in the fundus varied. They included multiple, variably sized serous pigment epithelial detachments, neurosensory retinal detachment, lipid deposition, patchy atrophy of the pigment epithelium and indistinct staining from decompensation of the posterior blood-retinal barrier on fluorescein angiography. In reality, the suspected PEDs proved to be polypoidal lesions of PCV when imaged with ICG angiography. Conclusions: The clinical diagnosis of CSC or PCV generally poses little challenge to the experienced retinal specialist. However, in CSC with persistent and/or recurrent exudation, a myriad of retinal pigment epithelial changes may evolve that make it difficult to differentiate these two entities. In such patients, ICG angiography is useful in differentiating CSC from PCV. An accurate clinical diagnosis is important since each of these entities, CSC and PCV, may differ in terms of their risk factors, natural course, and visual prognosis. Ophthalmology 2000;107:767–777 © 2000 by the American Academy of Ophthalmology. The clinical manifestations of central serous chorioretinopathy (CSC) have been well known for nearly a century.1–10 Although perplexed by its exact pathogenesis, ophthalmologists have little difficulty in recognizing the classic, clinical manifestations of the disorder. Patients are usually adult, emmetropic or slightly hyperopic males with a “type-A” behavioral pattern. They present with an exudative detachment of the neurosensory retina, often in association with multiple small serous pigment epithelial detachments (PEDs) and patchy retinal pigment epithelial atrophy.2 When there is doubt, a discrete or pinpoint leak at the level of the retinal pigment epithelium (RPE) noted on fluorescein angiography serves to confirm the diagnosis.
Originally received: July 13, 1999. Accepted: December 6, 1999. Manuscript no. 99365. From Vitreous-Retina-Macula Consultants, New York, New York. Supported by the LuEsther T. Mertz Retinal Research Laboratory of the Weill Medical College of Cornell University and The Macula Foundation, Inc. Reprint requests to: Lawrence A. Yannuzzi, MD, 519 East 72nd Street, Suite 203, New York, NY 10021. E-mail: [email protected] © 2000 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
Polypoidal choroidal vasculopathy (PCV) has been recognized for nearly two decades as a distinct exudative disorder of the macula.11–27 While its pathogenesis is also unclear, it is generally thought to be a primary abnormality of the choroid, consisting of a network of vessels with two distinct components: 1) a complex of branching vessels and 2) multiple, terminal, reddish-orange, aneurysmal or polypoidal lesions.11,12,16,20 Today, PCV is presumed to be a variant of choroidal neovascularization (CNV) or so-called polypoidal CNV. It is well known that the vascular abnormality is best imaged with indocyanine green (ICG) angiography as the longer wavelengths employed in this technique penetrate the RPE and the associated exudation with enhanced sensitivity and specificity.18,19 Originally, PCV was thought to present predominantly as a bilateral disorder affecting the peripapillary area of middle-aged black females with bullous serous and hemorrhagic detachments of the RPE and neurosensory retina.11–16 Some patients may even develop vitreous hemorrhage.11–15,20 Recently, Yannuzzi and co-workers20 reported on an expanded clinical spectrum of PCV; A mixed age, gender, and racial populaISSN 0161-6420/00/$–see front matter PII S0161-6420(99)00173-6
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Figure 1. A, clinical photograph of a 50-year-old female with a chronic neurosensory detachment of nine months duration. Note the lipid deposits at its margin. B, fluorescein angiogram revealed indistinct subretinal staining, consistent with decompensation of the retinal pigment epithelium (RPE). C, early ICG study revealed multiple focal areas of intense hyperfluorescence emerging from the inner choroidal circulation, external to the choriocapillaris. D, Very late ICG angiogram shows multiple aneurysmal staining or polypoidal lesions of polypoidal choroidal vasculopathy.
tion of patients was noted to be at risk of the disorder. Furthermore, solitary PCV lesions have been described in the macula as well as in the peripheral fundus.22 There is now a more widespread worldwide recognition of a higher prevalence and importance of the disorder.15,16,23–27 The typical or classic clinical presentation of CSC or PCV for retinal specialists poses little challenge. However, in some cases of CSC with persistence or recurrence of the neurosensory detachment, a myriad of secondary effects may develop at the level of the RPE, and fluorescein leakage
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may no longer be focal or discrete.10 Rather, a localized or diffuse area of RPE decompensation may evolve, resulting in gradual leakage through the posterior blood-retinal barrier and an indistinct zone of staining or a so-called “ooze.” With persistence of the detachment, lipid precipitation and even subretinal blood secondary to CNV may also occur in these patients.7,9,10 Furthermore, an isolated macular variant of PCV may have similar clinical and fluorescein angiographic characteristics which resemble CSC.10,20,21 These atypical cases of PCV involve small caliber vascular
Yannuzzi et al 䡠 PVC masquerading as CSC
Figure 2. A, clinical photograph of a 49-year-old Asian male with multiple pigment epithelial irregularities, resembling pigment epithelial detachments, beneath a neurosensory retinal detachment. B, fluorescein angiogram revealed a net of subretinal inner choroidal vessels terminating in aneurysmal or polypoidal lesions. C, early ICG angiogram revealed at least two focal areas of intense hyperfluorescence or “hot spots.” D, late ICG angiogram confirms the presence of a polypoidal vascular abnormality with branching vessels terminating in aneurysmal or polypoidal lesions. The polypoidal lesions at the inferior temporal aspect of the abnormality are “active polypoidal choroidal neovascularization,” accounting for the exudative changes (arrow).
abnormalities and may present exclusively with a serous detachment of the neurosensory retina. The polypoidal lesions may clinically and fluorescein angiographically resemble small PEDs. These cases of PCV may be said to “masquerade as CSC.” The purpose of this paper was 1) to report on a series of patients who were originally diagnosed as having CSC but who proved to have PCV with further evaluation and follow-up, and 2) to describe the clinical and angiographic findings essential for an accurate diagnosis.
Patients and Methods From January to October of 1999, thirteen patients who were originally suspected of having CSC with persistent or recurrent macular detachment were further evaluated and ultimately diagnosed as PCV. A complete ophthalmologic clinical examination, including slit-lamp biomicroscopy with a fundus contact lens and indirect ophthalmoscopy, was performed. Fluorescein angiography with 5 cc of 10% solution and an indocyanine green (ICG) angiogram with a 50 mg dose was obtained for each patient (Topcon
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Ophthalmology Volume 107, Number 4, April 2000 50IA fundus camera, Paramus, NJ). All patients were seen in the private subspecialty practice of the authors or in their affiliated institution, the LuEsther T. Mertz Retinal Research Center of the Manhattan Eye, Ear and Throat Hospital.
Patients The 13 study patients aged from 26 to 64 years (average 54). When further evaluated, several had a history of CSC for many years. There were nine males and four females. Eight patients were white, whereas five patients were of a pigmented race (1 black, 1 Asian, 1 Indian, 2 Hispanic). Four patients had bilateral disease (one had a disciform scar, one had very minimal RPE punctate atrophic changes, one had PCV in the fellow eye, and one had an epiretinal membrane). The other nine patients had no evidence of any pigmented epithelial or choroidal disease in the fellow eye. The primary visual acuity varied at the time of evaluation depending on the duration and the severity of the RPE and exudative degenerative changes. Three patients developed subretinal protein and eight had subretinal lipid and/or blood. Six patients had a neurosensory retinal detachment as the sole exudative manifestation at the time of evaluation, and the others had combined serous PEDs and retinal detachment.
Selected Case Descriptions Case 1. This 50-year-old white female had been diagnosed as having central serous chorioretinopathy 9 months earlier. Her visual acuity (VA) was 20/20 in the right eye and 20/80 in the left eye (Fig 1). There was a persistent, neurosensory detachment with lipid deposition in the left eye. The fellow eye was normal. The fluorescein angiogram revealed diffuse staining of the RPE interpreted as a chronic decompensation of the posterior blood-retinal barrier. The early-phase ICG angiogram revealed discrete areas of polypoidal intense hyperfluorescence emanating from medium size choroidal vessels. The late stage ICG angiogram (40 minutes after injection) showed a cluster of polypoidal lesions, two of which stained intensely (active polypoidal lesion).16 The remaining vascular complex faded in the very late stages of the study, but it still remained detectable in contrast to the more faintly staining extrachoroidal vascular space. Laser photocoagulation to the active polypoidal lesion but not to the entire vascular complex resulted in resolution of the detachment. Over a period of 7 years she required two additional laser treatments to leaking polypoidal lesions. At present, her macula is free of detachment and visual acuity is 20/25. Comment: This patient had a persistent neurosensory macula detachment with lipid deposition and indistinct fluorescein leakage. The ICG angiogram was essential in diagnosing PCV. Laser treatment of the active polypoidal lesions—not the entire PCV abnormality—was effective in resolving the detachment, with a good visual outcome. In this case the polypoidal lesions were external to the choriocapillaris. This anatomical location was easily determined because of the presence of the PCV on the early ICG and the obscuration of the lesion on the fluorescein study from staining of the choriocapillaris. Case 2. This 49-year-old Asian male presented with a visual disturbance in the left eye. The VA was 20/40 in the left eye, and there was metamorphopsia on Amsler grid testing. On fundus examination, there was a persistent neurosensory retinal detachment overlying multiple retinal pigment epithelial, shallow but discernible, elevations (Fig 2). These elevated RPE lesions were thought to be small PEDs. However, fluorescein and ICG angiography revealed a polypoidal CNV in the central macula. The fellow eye was normal.
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Comment: In this patient, the suspected PEDs proved to be the polypoidal lesions of PVC. The small caliber vessels in this PCV complex were seen more clearly on fluorescein angiography. The small, highly fluorescent fluorescein molecule is preferable to the minimally fluorescent large ICG dye for imaging small choroidal vessels. Above all, this PCV network must be immediately beneath the RPE or it would have been obscured by fluorescein leakage from the choriocapillaris. Case 3. This 56-year-old white male had three episodes of transient, unilateral visual disturbances from CSC. His VA was 20/30 in the right eye and 20/20 in the left eye. His clinical manifestations revealed a cluster of nummular elevations of the retinal pigment epithelium interpreted clinically as small, serous PEDs (Fig 3). A patch of fibrous metaplasia and a shallow neurosensory retinal elevation were also present in the central macula. His left eye was normal. The ICG angiogram, as well as the fluorescein angiogram, revealed a branching network of relatively small vessels in the inner choroid, terminating in the aneurysmal or polypoidal lesion of PCV. Only one of the polypoidal lesions was mildly staining (active polypoidal CNV lesion) in the late stage of the ICG angiogram. Comment: This patient experienced spontaneous resolution of recurrent detachments or a favorable natural course on three occasions in the past. The small caliber subpigment epithelial vessels and atrophy of the overlying RPE made the polypoidal CNV abnormality clearly visible on fluorescein angiography. Case 4. This 62-year-old Hispanic female presented with a history of poor vision in the left eye of several years’ duration and a recent decline in vision of the right eye. The VA was 20/40 in the right and 20/200 in the left. There was a disciform scar in the left eye and a large, persistent neurosensory retinal elevation in the right eye (Fig 4). Protein precipitates were present under the neurosensory retinal elevation, consistent with chronic detachment. There was also a faint deposit of lipid deposition near the disc. The fluorescein angiogram revealed indistinct staining superior to the disc at the upper limit of the neurosensory detachment. The ICG angiogram revealed a clearly evident PCV abnormality. Over a period of 4 months, the patient experienced subretinal hemorrhage beneath the papillomacular bundle from the polypoidal lesion. Three months later, gradual resolution of the blood and the exudate occurred with improvement of her visual acuity to the level of 20/50. Comment: This patient had a neurosensory retinal detachment with subretinal proteinacious and lipid precipitation typical of CSC. The ICG angiogram was needed to make an accurate diagnosis. In spite of subretinal hemorrhage, she experienced a favorable natural course. The disciform scar in the fellow eye was most likely due to combined polypoidal CNV and classic CNV. Case 5. This was a 26-year-old black male who was suspected of having CSC in his left eye of uncertain duration. His present visual disturbance was secondary to macular detachment. The VA was 20/20 in the right eye, and 20/25 in the left eye. There was a neurosensory foveal detachment with a mild degree of subretinal protein in the left eye (Fig 5). The right eye was normal. The fluorescein angiogram revealed some indistinct leakage consistent with multiple small serous PEDs. The ICG angiogram revealed a PCV and no choroidal hyperpermeability. Comment: CSC is rare in blacks. The ICG angiogram was useful in diagnosing PCV, which is more common in pigmented races. The absence of blood, lipid and RPE atrophy suggest that the macular detachment was not of long duration. Case 6. This is a 64-year-old white male who had a 19-year history of recurrent disturbance in the vision of each eye. When first seen 15 years ago, there was an exudative detachment of the neurosensory retina associated with lipid deposition in each eye. The fluorescein angiogram revealed only indistinct, diffuse pigment epi-
Yannuzzi et al 䡠 PVC masquerading as CSC
Figure 3. A, clinical photograph of a 56-year-old white male who had had three transient episodes of visual disturbance diagnosed as central serous chorioretinopathy. The macula was presently flat, overlying multiple, nummular elevations suggestive of small serous pigment epithelial detachments. At the center of this lesion there was a patch of fibrous metaplasia (arrow). B, fluorescein angiogram revealed a polypoidal choroidal abnormality with active staining of several polypoidal lesions. C, ICG angiogram confirmed the vascular nature of the abnormality.
thelial staining. Laser photocoagulation by a grid treatment to decompensating RPE leaks was carried out, with a gradual and eventually complete resolution of the edema and the lipid. During his most recent recurrent macular detachment, PCV was noted in the inferior nasal macula on ICG angiography (Fig 6). There were no areas of ICG choroidal hyperpermeability suggestive of CSC. Comment: This patient was diagnosed as having chronic CSC for many years. The ICG angiogram was needed to make the diagnosis of PCV. Laser treatment is generally not effective for chronic CSC with diffuse changes. Improvement following laser treatment in this patient may have been a clue to the presence of PCV. Case 7. This is a 60-year-old Indian male with a 2-year history of decreasing vision in the right eye. Vision was 20/100 in the right eye and 20/20 in the left eye. A serous detachment of the macula was eventually associated with lipid deposition and later complicated by subretinal hemorrhage (Fig 7). ICG angiography revealed
the true vascular nature of the lesion as polypoidal CNV in the central and inferior macula, clustered in a curvilinear fashion. Comment: The diagnosis of PCV was made in this patient after subretinal hemorrhage and an ICG angiogram was obtained.
Discussion For the classic presentation of central serous chorioretinopathy (CSC), there is little difficulty in establishing an accurate diagnosis.1–9 A young emmetropic or slightly hyperopic male adult with a high-risk behavioral pattern experiences typical central visual disturbances, such as micropsia, scotoma, and metamorphopsia from a neurosensory detachment that usually involves the fovea.2 There is a localized macular detachment and usually one or more
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Figure 4. A, clinical photograph of a 62-year-old Hispanic female who had a neurosensory detachment with multiple punctate areas of protein precipitation beneath the neurosensory retina in the central macula. There was a small fleck of lipid deposition at the supranasal edge of the neurosensory detachment (arrow). B, ICG angiogram revealed the presence of a polypoidal choroidal vascular abnormality in the superior temporal juxtapapillary region.
small pigment epithelial detachments (PEDs). At our institution, the clinical presentation is so familiar, we seldom use a fluorescein angiogram to confirm the diagnosis unless there is lipid, blood, or a grayish pigmentary disturbance to the subretinal area, suspicious of choroidal neovascularization (CNV). With persistence or recurrence of the detachment, a fluorescein angiogram is useful to delineate the exact manifestations, to confirm the diagnosis, and, in some cases, to serve as a possible guide for laser treatment to an eccentric, pinpoint or discrete leak at the level of the retinal pigment epithelium (RPE). However, with long standing or multiple, recurrent detachments, the clinical picture is more complex with the possible emergence of a myriad of secondary changes, including patchy RPE atrophy, atrophic pigment epithelial tracks, gravitating neurosensory detachments, lipid deposition, fibrous metaplasia, subretinal proteinacious precipitates, fibrin exudation, choroidal folds and even subretinal blood secondary to CNV.7,10 In these eyes, there is partial recovery of the presumed mechanical defect in the RPE that leads to the acute, focal, and intense leak into the subretinal space at or near the margin of a serous PED. With incomplete closure of the primary leak, a less distinct, gradual fluorescein leakage may emerge, sometimes masked by surrounding areas of pigment epithelial atrophic transmission or “window” defect and late scleral staining.9,10 Polypoidal choroidal vasculopathy (PCV), now thought to be a variant of choroidal neovascularization or polypoidal CNV, is also relatively simple to diagnose in most cases.12–20 When PCV involves large caliber vessels terminating in reddish-orange, aneurysmal or polypoidal dilatations, the vascular abnormality may be seen clinically through slightly atrophic pigment epithelium, even when the vessels are dormant or quiescent, free of serosanguineous complications. In such eyes, the fluorescein angiogram can sometimes confirm the diagnosis, but the ICG angiogram is generally regarded as the preferred method for imaging these choroidal vessels, particularly when they are external
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to the choriocapillaris, such as in case #1. The longer wavelengths used in ICG angiography penetrate the RPE and any associated serosanguineous complications with higher levels of sensitivity and specificity.18,19,28 Cases of CSC such as those in this series, with persistent or recurrent detachment, pose a more difficult clinical challenge. The frequency of PCV masquerading as CSC could not be determined with reasonable accuracy because our cases were derived from new as well as long term patients. In these eyes, there may be underlying polypoidal CNV masquerading as chronic CSC. ICG angiography is useful in establishing a correct diagnosis. With this diagnostic adjunct, there is a greater chance of imaging the precise nature, location and extent of the polypoidal CNV. The PCV lesion remains as occult CNV and ICG angiography confirms its presence. Furthermore, the ICG angiogram is also of value in recording the absence of multifocal areas of choroidal hyperpermeability (late ICG staining) which have no clinical or fluorescein angiographic counterpart. These zones of choroidal leakage, known to be indicative of CSC, are not seen in PCV (Fig 8).29 –31 None of the cases presented in this series revealed signs of choroidal hyperpermeability on ICG angiography. Although ICG angiography is generally the accepted standard for imaging PCV, the fluorescein angiogram curiously was adequate, if not better, in detecting the polypoidal CNV in two of our cases (cases #2 and #3). In each of these cases there was a small caliber PCV vascular network terminating in multiple, polypoidal lesions. While it is not known exactly why fluorescein angiography images the PCV complex with such clear definition, the small caliber of the branching vessels is likely to be a factor. Fluorescein also images the small capillaries of well-demarcated or so-called classic CNV with better definition than ICG angiography.32 The larger ICG molecule and dye protein bioconjugate with reduced natural fluorescence is less suitable than the smaller, highly fluorescent fluorescein molecule. Some atrophy to the RPE from antecedent detachment
Yannuzzi et al 䡠 PVC masquerading as CSC
Figure 5. A, clinical photograph of a 26-years-old black male with a neurosensory retinal elevation in the central macula. There are multiple protein precipitates under the neurosensory retinal elevation. B, fluorescein angiogram revealed multifocal areas of indistinct subretinal staining, suggestive of small serous pigment epithelial detachments. C, ICG showed the presence of a polypoidal choroidal vascular abnormality with multiple, aneurysmal-like polypoidal lesions beneath the fovea.
is also likely to make the PCV complex clearer with fluorescein angiography in these two patients. One other consideration could be proliferation of the PCV lesion between the RPE and Bruch’s membrane or anterior to the RPE in the subretinal space. The PCV in this anatomical location would not be masked or obscured by choriocapillaris leakage. Supporting this assumption are clinical pathology correlations which reveal large venular-like vessels immediately beneath the RPE.15 Certain demographic and clinical factors are also useful to identify PCV in these patients suspected of having chronic CSC. The age range was 26 –59 (average 54 years), which is consistent with CSC and PCV. However, a higher level of suspicion for PCV masquerading as CSC existed in case #5, the 26-year-old black male. This case represents an
obvious demographic inconsistency for CSC, a black patient under the age of 30 years. At our institution, there has been only one black patient under the age of 35 years seen in the past 35 years in several hundred cases of CSC. A patient with CSC under the age of 30 years is very rare in our experience as well. The sex of the study cases was again consistent with either entity (nine males and four females). Although CSC is predominantly a disorder of males, chronic cases, particularly in patients over the age of 50 years, do not show much of a sex predilection.28 Lipid and particularly blood beneath the neurosensory detachment is another factor heightening the clinical suspicion of PCV rather than CSC. Five study patients had detachment with associated subretinal lipid. Six of the cases
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Figure 6. ICG angiogram of a 64-year-old male that reveals a polypoidal choroidal vascular abnormality with branching vessels terminating in multiple polypoidal lesions.
eventually became associated with subretinal hemorrhage, in one instance after several weeks of detachment (Case #4); months after detachment (Cases #6, #9), and even several years after multiple, recurrent neurosensory detachments (Case #8, #12). Yet, chronic neurosensory detachments in CSC may be associated with lipid deposition as large li-
pophilic molecules accumulate intraretinally and subretinally, coincident with longevity.7,9 CNV and subretinal blood are also potential complications in CSC.7,9,10 However, lipid and bleeding are paramount features of PCV.12,15,16,20 In our cases, it was not always possible to determine whether the PCV was a primary pathogenetic factor for the macular detachment or a secondary manifestation induced by exudation or nonspecific disturbance of the RPE. Only four cases had bilateral disease (Case #4, #7, #8, and #13). One had a disciform scar; one had PCV, one had non-specific RPE changes, and one had an epiretinal membrane in the fellow eye. The patient with the disciform scar in the fellow eye most probably had PCV which evolved into a mix form of CNV. CSC has a marked tendency to be bilateral with non exudative changes present in both eyes in more than 80% of the cases in our files.7,9 It is not uncommon for PCV on the other hand to be unilateral.15,16 So, unilateral presentations should alert the clinician to the possibility of PCV in an eye suspected of having chronic CSC. Seven of the study cases had serous PEDs which are commonly seen with CSC and PCV. In some eyes, serous PEDs can be indistinguishable clinically from a small caliber polypoidal vascular abnormality. Because of their vascular nature, the polypoidal lesions tend to be reddishorange in color, but not always. When the overlying RPE is intact, it may mask the vascular appearance of the lesions, particularly if the polypoidal-CNV involves relatively small vessels. The principle way of differentiating a small serous PED from a polypoidal lesion is with ICG angiography. Knowledge of the fluorescein and ICG angiogram characteristics of a serous PED is essential in differentiating CSC from PCV. Late staining of the PED is seen with fluorescein
Figure 7. A, clinical photograph of a 60 year-old-Indian male with a 2 year history of serosanguineous detachment of the macula in the right eye. A semi-circle of lipid exudation surrounds the detachment. B, ICG angiography revealed polypoidal vascular choroidal lesions in the central macula and clustered in a curvilinear fashion in the inferior macula.
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Yannuzzi et al 䡠 PVC masquerading as CSC
Figure 8. A, clinical photograph of a patient with a neurosensory detachment involving the central macula. There are a few minor and non specific pigment epithelial changes. B, fluorescein angiography showed a slight degree of subretinal, indistinct leakage beneath the detachment. C, ICG angiography revealed multiple areas of choroidal staining or hyperpermeability characteristic of central serous chorioretinopathy.
angiography; whereas, the ICG angiogram shows hypofluorescence. In contrast the polypoidal lesion is hyperfluorescent with ICG angiography because of its vascular nature. There are, however, three exceptions. A very large PED in CSC, laden with fibrin exudation, may reveal a mild degree of subpigment epithelial hyperfluorescence and a notable ring of staining at its margins with ICG angiography.28,31 The fibrin has an affinity for the ICG dye and for the dye protein bio-conjugate. Another exception is the PED that overlies an area of choroidal hyperpermeability.30 This situation results in choroidal transmission of hyperfluorescence through the subpigment epithelial space, a form of pseudo-pigment epithelial fluorescence. It is important to keep in mind that a PCV lesion may exist under a PED. The portion of the PED overlying the PCV lesion will be hypofluorescent. If the PCV lesion is actually leaking, the ICG dye may extend or “pool” into the subpigment epithelial
space.20,31 Finally, ICG angiography is also of importance in differentiating PCV from CSC on the basis of multifocal areas of choroidal hyperpermeability. As mentioned above, there is a consistent finding in CSC and not in manifestations of PCV. The importance for an accurate clinical distinction between CSC and PCV is obvious. Each entity has its own independent set of demographic risk files and clinical and angiographic features. They may also differ in their natural course, visual prognosis, and response to treatment.2,3,8,9,12,20 Actually, the natural course of each disorder is not well known; nor is there a clearly established treatment based on prospective, randomized clinical trials. Yet, most retinal specialists will consider and employ laser photocoagulation treatment for CSC when there is a persistent detachment, particularly when associated with decompensating RPE, visual decline and an eccentric focal RPE leak.9,10 The assumption is
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Ophthalmology Volume 107, Number 4, April 2000 Table 1. Summary of cases
Case
Age
Sex
Race
Eye
Fellow eye
1 2 3 4 5 6 7 8 9 10 11 12 13
50 49 56 62 26 69 60 64 63 57 37 54 51
F M M F M M F M M M F F M
W A W H B H I W W W W W W
OS OS OD OD OS OS OD OD OS OS OD OS OS
n n n Scar n Prosthesis n PCV n n n n ERM
Clinical Examination
Fluorescein Angio
ICG Angio
Lipid
Blood
Protein
Staining
PED
PCV
Hyperper
PCV
X — — X — X X X — — X — —
— — — X — X X X X — — X —
— — — X X — — — — X — — —
X — — X X X X X X X X X X
— X X — X — X — X X X — —
— X X — — — — — — — — — —
— — — — — — — — — — — — —
X X X X X X X X X X X X X
A ⫽ Asian; B ⫽ Black; ERM ⫽ epiretinal membrane; F ⫽ female; fluorescein angio ⫽ fluorescein angiography; H ⫽ Hispanic; hyperper ⫽ choroidal hyperpermeability; I ⫽ Indian; ICG angio ⫽ ICG angiography; M ⫽ male; n ⫽ normal; OS ⫽ left eye; OD ⫽ right eye; PCV ⫽ polypoidal choroidal vasculopathy; PED ⫽ pigment epithelium detachment; scar ⫽ disciform scar; W ⫽ White.
that a more accelerated resolution of the neurosensory detachment is likely to preserve or restore central vision and possibly decrease the recurrence rate. Laser treatment of chronic CSC has not been generally successful.7,10 Laser photocoagulation treatment of active polypoidal lesions, accounting for serosanguineous detachments of the macula, has also been used empirically to accelerate the resolution of subfoveal blood and exudate. Such treatment is also presumptive, anecdotal and rational, yet unproven in terms of its efficacy and safety.12,16,20 Although two patients (cases #1 and #8) with chronic detachment had resolution of the detachment and improvement of vision after laser treatment, other patients (case #3 and case #4) had a favorable natural course without laser intervention. Future studies are needed to determine the exact role of laser treatment in CSC, PVC, and the peculiar variant of PCV which masquerades as chronic CSC described in this series. In summary, patients with CSC may become associated with clinical and fluorescein angiographic manifestations which are indistinguishable from PCV. In such cases, ICG angiography should be performed to establish a more definitive diagnosis, particularly in 1) patients who are generally not at risk of CSC on the basis age, sex, or race, 2) eyes with persistent detachments associated with lipid, and 3) recurrent detachments with subretinal blood. Accurate diagnosis is important to the clinician in the management of these patients.
References 1. Gass JDM. Pathogenesis of disciform detachment of the neuroepithelium. II. Idiopathic central serous choroidopathy. Am J Ophthalmol 1967;63:587– 615. 2. Yannuzzi LA. Type A behavior and central serous chorioretinopathy. Trans Am Ophthalmol Soc 1986;84:799 – 845. 3. Yannuzzi LA, Gitter KA, Schatz H. The Macula: A Comprehensive Text and Atlas. Baltimore: Williams & Wilkins, 1979; 145– 65. 4. Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 4th ed. St. Louis: Mosby, 1997;52–70.
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5. Burton TC. Central serous retinopathy. In: Blodi FC, ed. Current Concepts in Ophthalmology. Vol III. St. Louis: Mosby, 1972;1–28. 6. Schatz H. Central serous chorioretinopathy and serous detachment of the retinal pigment epithelium. Int Ophthalmol Clin 1975;15:159 – 68. 7. Yannuzzi LA, Shakin JL, Fisher YL, Altomonte MA. Peripheral retinal detachments and retinal pigment epithelial atrophic tracts secondary to central serous pigment epitheliopathy. Ophthalmology 1984;91:1554 –72. 8. Levine R, Brucker AJ, Robinson F. Long-term follow-up of idiopathic central serous chorioretinopathy by fluorescein angiography. Ophthalmology 1989;96:854 –9. 9. Yannuzzi LA, ed. Laser Photocoagulation of the Macula. Philadelphia: J.B. Lippincott, 1989;1–12. 10. Yannuzzi LA, Slakter JS, Kaufman SR, Gupta K. Laser treatment of diffuse retinal pigment epitheliopathy. Eur J Ophthalmol 1992;2:103–14. 11. Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina 1990;10: 1– 8. 12. Kleiner RC, Brucker AJ, Johnston RL. The posterior uveal bleeding syndrome. Retina 1990;10:9 –17. 13. Stern RM, Zakov ZN, Zegarra H, Gutman FA. Multiple recurrent serosanguineous retinal pigment epithelial detachments in black women. Am J Ophthalmol 1985;100:560 –9. 14. Perkovich BT, Zakov ZN, Berlin LA, et al. An update on multiple recurrent serosanguineous retinal pigment epithelial detachments in black women. Retina 1990;10:18 –26. 15. Uyama M, Matsubara T, Fukushima I, et al. Idiopathic polypoidal choroidal vasculopathy in Japanese patients. Arch Ophthalmol 1999;117:1035– 42. 16. Yannuzzi LA, Wong DW, Sforzolini BS, et al. Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration. Arch Ophthalmol 1999;117:1503–10. 17. Ross RD, Gitter KA, Cohen G, Schomaker KS. Idiopathic polypoidal choroidal vasculopathy associated with retinal arterial macroaneurysm and hypertensive retinopathy. Retina 1996;16:105–11. 18. Spaide RF, Yannuzzi LA, Slakter JS, et al. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina 1995;15:100 –10.
Yannuzzi et al 䡠 PVC masquerading as CSC 19. Yannuzzi LA, Slakter JS, Sorenson JA, et al. Digital indocyanine green videoangiography and choroidal neovascularization. Retina 1992;12:191–223. 20. Yannuzzi LA, Ciardella A, Spaide RF, et al. The expanding clinical spectrum of idiopathic polypoidal choroidal vasculopathy. Arch Ophthalmol 1997;115:478 – 85. 21. Moorthy RS, Lyon AT, Rabb MF, et al. Idiopathic polypoidal choroidal vasculopathy of the macula. Ophthalmology 1998; 105:1380 –5. 22. Yannuzzi LA, Nogueira FB, Spaide RF, et al. Idiopathic polypoidal choroidal vasculopathy: a peripheral lesion [letter]. Arch Ophthalmol 1998;116:382–3. 23. Spraul CW, Grossniklaus HE, Lang GK. Idiopathische polypo¨se choroidale Vaskulopathie (IPCV) [Eng. Abstr.]. Klin Monatsbl Augenheilkd 1997;210:405– 6. 24. Gomez-Ulla F, Gonzalez F, Torreiro MG. Diode laser photocoagulation in idiopathic polypoidal choroidal vasculopathy. Retina 1998;18:481–3. 25. Schneider U, Gelisken F, Kreissig I. Indocyanine green angiography and idiopathic polypoidal choroidal vasculopathy. Br J Ophthalmol 1998;82:98 –9. 26. Iijima H, Imai M, Gohdo T, Tsukahara S. Optical coherence
27.
28. 29. 30. 31.
32.
tomography of idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol 1999;127:301–5. Yannuzzi LA, Nogueira FB, Spaide RF, et al. Valoracion de la calidad y padrones de utilizacion en los sistemas provedores de atencion sanitaria [Editorial]. Arch Ophthalmol (Spanish) 1998;116:180 –1. Spaide RF, Hall L, Haas A, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina 1996;16:203–13. Guyer DR, Yannuzzi LA, Slakter JS, et al. Digital indocyanine green videoangiography of central serous chorioretinopathy. Arch Ophthalmol 1994;112:1057– 62. Guyer DR. Central serous chorioretinopathy. In: Yannuzzi LA, Flower RW, Slakter JS, eds. Indocyanine Green Angiography. St. Louis: Mosby, 1997;297–304. Spaide RF. ICG videoangiography of idiopathic polypoidal choroidal vasculopathy. In: Yannuzzi LA, Flower RW, Slakter JS, eds. Indocyanine Green Angiography. St. Louis: Mosby, 1997;329 – 40. Guyer DR, Yannuzzi LA, Slakter JS, et al. Digital indocyanine-green videoangiography of occult choroidal neovascularization. Ophthalmology 1994;101:1727–37.
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Originally received: July 13, 1999. Accepted: December 6, 1999. Manuscript no. 99365. From Vitreous-Retina-Macula Consultants, New York, New York. Supported by the LuEsther T. Mertz Retinal Research Laboratory of the Weill Medical College of Cornell University and The Macula Foundation, Inc. Reprint requests to: Lawrence A. Yannuzzi, MD, 519 East 72nd Street, Suite 203, New York, NY 10021. E-mail: [email protected] © 2000 by the American Academy of Ophthalmology Published by Elsevier Science Inc.
Polypoidal choroidal vasculopathy (PCV) has been recognized for nearly two decades as a distinct exudative disorder of the macula.11–27 While its pathogenesis is also unclear, it is generally thought to be a primary abnormality of the choroid, consisting of a network of vessels with two distinct components: 1) a complex of branching vessels and 2) multiple, terminal, reddish-orange, aneurysmal or polypoidal lesions.11,12,16,20 Today, PCV is presumed to be a variant of choroidal neovascularization (CNV) or so-called polypoidal CNV. It is well known that the vascular abnormality is best imaged with indocyanine green (ICG) angiography as the longer wavelengths employed in this technique penetrate the RPE and the associated exudation with enhanced sensitivity and specificity.18,19 Originally, PCV was thought to present predominantly as a bilateral disorder affecting the peripapillary area of middle-aged black females with bullous serous and hemorrhagic detachments of the RPE and neurosensory retina.11–16 Some patients may even develop vitreous hemorrhage.11–15,20 Recently, Yannuzzi and co-workers20 reported on an expanded clinical spectrum of PCV; A mixed age, gender, and racial populaISSN 0161-6420/00/$–see front matter PII S0161-6420(99)00173-6
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Figure 1. A, clinical photograph of a 50-year-old female with a chronic neurosensory detachment of nine months duration. Note the lipid deposits at its margin. B, fluorescein angiogram revealed indistinct subretinal staining, consistent with decompensation of the retinal pigment epithelium (RPE). C, early ICG study revealed multiple focal areas of intense hyperfluorescence emerging from the inner choroidal circulation, external to the choriocapillaris. D, Very late ICG angiogram shows multiple aneurysmal staining or polypoidal lesions of polypoidal choroidal vasculopathy.
tion of patients was noted to be at risk of the disorder. Furthermore, solitary PCV lesions have been described in the macula as well as in the peripheral fundus.22 There is now a more widespread worldwide recognition of a higher prevalence and importance of the disorder.15,16,23–27 The typical or classic clinical presentation of CSC or PCV for retinal specialists poses little challenge. However, in some cases of CSC with persistence or recurrence of the neurosensory detachment, a myriad of secondary effects may develop at the level of the RPE, and fluorescein leakage
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may no longer be focal or discrete.10 Rather, a localized or diffuse area of RPE decompensation may evolve, resulting in gradual leakage through the posterior blood-retinal barrier and an indistinct zone of staining or a so-called “ooze.” With persistence of the detachment, lipid precipitation and even subretinal blood secondary to CNV may also occur in these patients.7,9,10 Furthermore, an isolated macular variant of PCV may have similar clinical and fluorescein angiographic characteristics which resemble CSC.10,20,21 These atypical cases of PCV involve small caliber vascular
Yannuzzi et al 䡠 PVC masquerading as CSC
Figure 2. A, clinical photograph of a 49-year-old Asian male with multiple pigment epithelial irregularities, resembling pigment epithelial detachments, beneath a neurosensory retinal detachment. B, fluorescein angiogram revealed a net of subretinal inner choroidal vessels terminating in aneurysmal or polypoidal lesions. C, early ICG angiogram revealed at least two focal areas of intense hyperfluorescence or “hot spots.” D, late ICG angiogram confirms the presence of a polypoidal vascular abnormality with branching vessels terminating in aneurysmal or polypoidal lesions. The polypoidal lesions at the inferior temporal aspect of the abnormality are “active polypoidal choroidal neovascularization,” accounting for the exudative changes (arrow).
abnormalities and may present exclusively with a serous detachment of the neurosensory retina. The polypoidal lesions may clinically and fluorescein angiographically resemble small PEDs. These cases of PCV may be said to “masquerade as CSC.” The purpose of this paper was 1) to report on a series of patients who were originally diagnosed as having CSC but who proved to have PCV with further evaluation and follow-up, and 2) to describe the clinical and angiographic findings essential for an accurate diagnosis.
Patients and Methods From January to October of 1999, thirteen patients who were originally suspected of having CSC with persistent or recurrent macular detachment were further evaluated and ultimately diagnosed as PCV. A complete ophthalmologic clinical examination, including slit-lamp biomicroscopy with a fundus contact lens and indirect ophthalmoscopy, was performed. Fluorescein angiography with 5 cc of 10% solution and an indocyanine green (ICG) angiogram with a 50 mg dose was obtained for each patient (Topcon
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Ophthalmology Volume 107, Number 4, April 2000 50IA fundus camera, Paramus, NJ). All patients were seen in the private subspecialty practice of the authors or in their affiliated institution, the LuEsther T. Mertz Retinal Research Center of the Manhattan Eye, Ear and Throat Hospital.
Patients The 13 study patients aged from 26 to 64 years (average 54). When further evaluated, several had a history of CSC for many years. There were nine males and four females. Eight patients were white, whereas five patients were of a pigmented race (1 black, 1 Asian, 1 Indian, 2 Hispanic). Four patients had bilateral disease (one had a disciform scar, one had very minimal RPE punctate atrophic changes, one had PCV in the fellow eye, and one had an epiretinal membrane). The other nine patients had no evidence of any pigmented epithelial or choroidal disease in the fellow eye. The primary visual acuity varied at the time of evaluation depending on the duration and the severity of the RPE and exudative degenerative changes. Three patients developed subretinal protein and eight had subretinal lipid and/or blood. Six patients had a neurosensory retinal detachment as the sole exudative manifestation at the time of evaluation, and the others had combined serous PEDs and retinal detachment.
Selected Case Descriptions Case 1. This 50-year-old white female had been diagnosed as having central serous chorioretinopathy 9 months earlier. Her visual acuity (VA) was 20/20 in the right eye and 20/80 in the left eye (Fig 1). There was a persistent, neurosensory detachment with lipid deposition in the left eye. The fellow eye was normal. The fluorescein angiogram revealed diffuse staining of the RPE interpreted as a chronic decompensation of the posterior blood-retinal barrier. The early-phase ICG angiogram revealed discrete areas of polypoidal intense hyperfluorescence emanating from medium size choroidal vessels. The late stage ICG angiogram (40 minutes after injection) showed a cluster of polypoidal lesions, two of which stained intensely (active polypoidal lesion).16 The remaining vascular complex faded in the very late stages of the study, but it still remained detectable in contrast to the more faintly staining extrachoroidal vascular space. Laser photocoagulation to the active polypoidal lesion but not to the entire vascular complex resulted in resolution of the detachment. Over a period of 7 years she required two additional laser treatments to leaking polypoidal lesions. At present, her macula is free of detachment and visual acuity is 20/25. Comment: This patient had a persistent neurosensory macula detachment with lipid deposition and indistinct fluorescein leakage. The ICG angiogram was essential in diagnosing PCV. Laser treatment of the active polypoidal lesions—not the entire PCV abnormality—was effective in resolving the detachment, with a good visual outcome. In this case the polypoidal lesions were external to the choriocapillaris. This anatomical location was easily determined because of the presence of the PCV on the early ICG and the obscuration of the lesion on the fluorescein study from staining of the choriocapillaris. Case 2. This 49-year-old Asian male presented with a visual disturbance in the left eye. The VA was 20/40 in the left eye, and there was metamorphopsia on Amsler grid testing. On fundus examination, there was a persistent neurosensory retinal detachment overlying multiple retinal pigment epithelial, shallow but discernible, elevations (Fig 2). These elevated RPE lesions were thought to be small PEDs. However, fluorescein and ICG angiography revealed a polypoidal CNV in the central macula. The fellow eye was normal.
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Comment: In this patient, the suspected PEDs proved to be the polypoidal lesions of PVC. The small caliber vessels in this PCV complex were seen more clearly on fluorescein angiography. The small, highly fluorescent fluorescein molecule is preferable to the minimally fluorescent large ICG dye for imaging small choroidal vessels. Above all, this PCV network must be immediately beneath the RPE or it would have been obscured by fluorescein leakage from the choriocapillaris. Case 3. This 56-year-old white male had three episodes of transient, unilateral visual disturbances from CSC. His VA was 20/30 in the right eye and 20/20 in the left eye. His clinical manifestations revealed a cluster of nummular elevations of the retinal pigment epithelium interpreted clinically as small, serous PEDs (Fig 3). A patch of fibrous metaplasia and a shallow neurosensory retinal elevation were also present in the central macula. His left eye was normal. The ICG angiogram, as well as the fluorescein angiogram, revealed a branching network of relatively small vessels in the inner choroid, terminating in the aneurysmal or polypoidal lesion of PCV. Only one of the polypoidal lesions was mildly staining (active polypoidal CNV lesion) in the late stage of the ICG angiogram. Comment: This patient experienced spontaneous resolution of recurrent detachments or a favorable natural course on three occasions in the past. The small caliber subpigment epithelial vessels and atrophy of the overlying RPE made the polypoidal CNV abnormality clearly visible on fluorescein angiography. Case 4. This 62-year-old Hispanic female presented with a history of poor vision in the left eye of several years’ duration and a recent decline in vision of the right eye. The VA was 20/40 in the right and 20/200 in the left. There was a disciform scar in the left eye and a large, persistent neurosensory retinal elevation in the right eye (Fig 4). Protein precipitates were present under the neurosensory retinal elevation, consistent with chronic detachment. There was also a faint deposit of lipid deposition near the disc. The fluorescein angiogram revealed indistinct staining superior to the disc at the upper limit of the neurosensory detachment. The ICG angiogram revealed a clearly evident PCV abnormality. Over a period of 4 months, the patient experienced subretinal hemorrhage beneath the papillomacular bundle from the polypoidal lesion. Three months later, gradual resolution of the blood and the exudate occurred with improvement of her visual acuity to the level of 20/50. Comment: This patient had a neurosensory retinal detachment with subretinal proteinacious and lipid precipitation typical of CSC. The ICG angiogram was needed to make an accurate diagnosis. In spite of subretinal hemorrhage, she experienced a favorable natural course. The disciform scar in the fellow eye was most likely due to combined polypoidal CNV and classic CNV. Case 5. This was a 26-year-old black male who was suspected of having CSC in his left eye of uncertain duration. His present visual disturbance was secondary to macular detachment. The VA was 20/20 in the right eye, and 20/25 in the left eye. There was a neurosensory foveal detachment with a mild degree of subretinal protein in the left eye (Fig 5). The right eye was normal. The fluorescein angiogram revealed some indistinct leakage consistent with multiple small serous PEDs. The ICG angiogram revealed a PCV and no choroidal hyperpermeability. Comment: CSC is rare in blacks. The ICG angiogram was useful in diagnosing PCV, which is more common in pigmented races. The absence of blood, lipid and RPE atrophy suggest that the macular detachment was not of long duration. Case 6. This is a 64-year-old white male who had a 19-year history of recurrent disturbance in the vision of each eye. When first seen 15 years ago, there was an exudative detachment of the neurosensory retina associated with lipid deposition in each eye. The fluorescein angiogram revealed only indistinct, diffuse pigment epi-
Yannuzzi et al 䡠 PVC masquerading as CSC
Figure 3. A, clinical photograph of a 56-year-old white male who had had three transient episodes of visual disturbance diagnosed as central serous chorioretinopathy. The macula was presently flat, overlying multiple, nummular elevations suggestive of small serous pigment epithelial detachments. At the center of this lesion there was a patch of fibrous metaplasia (arrow). B, fluorescein angiogram revealed a polypoidal choroidal abnormality with active staining of several polypoidal lesions. C, ICG angiogram confirmed the vascular nature of the abnormality.
thelial staining. Laser photocoagulation by a grid treatment to decompensating RPE leaks was carried out, with a gradual and eventually complete resolution of the edema and the lipid. During his most recent recurrent macular detachment, PCV was noted in the inferior nasal macula on ICG angiography (Fig 6). There were no areas of ICG choroidal hyperpermeability suggestive of CSC. Comment: This patient was diagnosed as having chronic CSC for many years. The ICG angiogram was needed to make the diagnosis of PCV. Laser treatment is generally not effective for chronic CSC with diffuse changes. Improvement following laser treatment in this patient may have been a clue to the presence of PCV. Case 7. This is a 60-year-old Indian male with a 2-year history of decreasing vision in the right eye. Vision was 20/100 in the right eye and 20/20 in the left eye. A serous detachment of the macula was eventually associated with lipid deposition and later complicated by subretinal hemorrhage (Fig 7). ICG angiography revealed
the true vascular nature of the lesion as polypoidal CNV in the central and inferior macula, clustered in a curvilinear fashion. Comment: The diagnosis of PCV was made in this patient after subretinal hemorrhage and an ICG angiogram was obtained.
Discussion For the classic presentation of central serous chorioretinopathy (CSC), there is little difficulty in establishing an accurate diagnosis.1–9 A young emmetropic or slightly hyperopic male adult with a high-risk behavioral pattern experiences typical central visual disturbances, such as micropsia, scotoma, and metamorphopsia from a neurosensory detachment that usually involves the fovea.2 There is a localized macular detachment and usually one or more
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Figure 4. A, clinical photograph of a 62-year-old Hispanic female who had a neurosensory detachment with multiple punctate areas of protein precipitation beneath the neurosensory retina in the central macula. There was a small fleck of lipid deposition at the supranasal edge of the neurosensory detachment (arrow). B, ICG angiogram revealed the presence of a polypoidal choroidal vascular abnormality in the superior temporal juxtapapillary region.
small pigment epithelial detachments (PEDs). At our institution, the clinical presentation is so familiar, we seldom use a fluorescein angiogram to confirm the diagnosis unless there is lipid, blood, or a grayish pigmentary disturbance to the subretinal area, suspicious of choroidal neovascularization (CNV). With persistence or recurrence of the detachment, a fluorescein angiogram is useful to delineate the exact manifestations, to confirm the diagnosis, and, in some cases, to serve as a possible guide for laser treatment to an eccentric, pinpoint or discrete leak at the level of the retinal pigment epithelium (RPE). However, with long standing or multiple, recurrent detachments, the clinical picture is more complex with the possible emergence of a myriad of secondary changes, including patchy RPE atrophy, atrophic pigment epithelial tracks, gravitating neurosensory detachments, lipid deposition, fibrous metaplasia, subretinal proteinacious precipitates, fibrin exudation, choroidal folds and even subretinal blood secondary to CNV.7,10 In these eyes, there is partial recovery of the presumed mechanical defect in the RPE that leads to the acute, focal, and intense leak into the subretinal space at or near the margin of a serous PED. With incomplete closure of the primary leak, a less distinct, gradual fluorescein leakage may emerge, sometimes masked by surrounding areas of pigment epithelial atrophic transmission or “window” defect and late scleral staining.9,10 Polypoidal choroidal vasculopathy (PCV), now thought to be a variant of choroidal neovascularization or polypoidal CNV, is also relatively simple to diagnose in most cases.12–20 When PCV involves large caliber vessels terminating in reddish-orange, aneurysmal or polypoidal dilatations, the vascular abnormality may be seen clinically through slightly atrophic pigment epithelium, even when the vessels are dormant or quiescent, free of serosanguineous complications. In such eyes, the fluorescein angiogram can sometimes confirm the diagnosis, but the ICG angiogram is generally regarded as the preferred method for imaging these choroidal vessels, particularly when they are external
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to the choriocapillaris, such as in case #1. The longer wavelengths used in ICG angiography penetrate the RPE and any associated serosanguineous complications with higher levels of sensitivity and specificity.18,19,28 Cases of CSC such as those in this series, with persistent or recurrent detachment, pose a more difficult clinical challenge. The frequency of PCV masquerading as CSC could not be determined with reasonable accuracy because our cases were derived from new as well as long term patients. In these eyes, there may be underlying polypoidal CNV masquerading as chronic CSC. ICG angiography is useful in establishing a correct diagnosis. With this diagnostic adjunct, there is a greater chance of imaging the precise nature, location and extent of the polypoidal CNV. The PCV lesion remains as occult CNV and ICG angiography confirms its presence. Furthermore, the ICG angiogram is also of value in recording the absence of multifocal areas of choroidal hyperpermeability (late ICG staining) which have no clinical or fluorescein angiographic counterpart. These zones of choroidal leakage, known to be indicative of CSC, are not seen in PCV (Fig 8).29 –31 None of the cases presented in this series revealed signs of choroidal hyperpermeability on ICG angiography. Although ICG angiography is generally the accepted standard for imaging PCV, the fluorescein angiogram curiously was adequate, if not better, in detecting the polypoidal CNV in two of our cases (cases #2 and #3). In each of these cases there was a small caliber PCV vascular network terminating in multiple, polypoidal lesions. While it is not known exactly why fluorescein angiography images the PCV complex with such clear definition, the small caliber of the branching vessels is likely to be a factor. Fluorescein also images the small capillaries of well-demarcated or so-called classic CNV with better definition than ICG angiography.32 The larger ICG molecule and dye protein bioconjugate with reduced natural fluorescence is less suitable than the smaller, highly fluorescent fluorescein molecule. Some atrophy to the RPE from antecedent detachment
Yannuzzi et al 䡠 PVC masquerading as CSC
Figure 5. A, clinical photograph of a 26-years-old black male with a neurosensory retinal elevation in the central macula. There are multiple protein precipitates under the neurosensory retinal elevation. B, fluorescein angiogram revealed multifocal areas of indistinct subretinal staining, suggestive of small serous pigment epithelial detachments. C, ICG showed the presence of a polypoidal choroidal vascular abnormality with multiple, aneurysmal-like polypoidal lesions beneath the fovea.
is also likely to make the PCV complex clearer with fluorescein angiography in these two patients. One other consideration could be proliferation of the PCV lesion between the RPE and Bruch’s membrane or anterior to the RPE in the subretinal space. The PCV in this anatomical location would not be masked or obscured by choriocapillaris leakage. Supporting this assumption are clinical pathology correlations which reveal large venular-like vessels immediately beneath the RPE.15 Certain demographic and clinical factors are also useful to identify PCV in these patients suspected of having chronic CSC. The age range was 26 –59 (average 54 years), which is consistent with CSC and PCV. However, a higher level of suspicion for PCV masquerading as CSC existed in case #5, the 26-year-old black male. This case represents an
obvious demographic inconsistency for CSC, a black patient under the age of 30 years. At our institution, there has been only one black patient under the age of 35 years seen in the past 35 years in several hundred cases of CSC. A patient with CSC under the age of 30 years is very rare in our experience as well. The sex of the study cases was again consistent with either entity (nine males and four females). Although CSC is predominantly a disorder of males, chronic cases, particularly in patients over the age of 50 years, do not show much of a sex predilection.28 Lipid and particularly blood beneath the neurosensory detachment is another factor heightening the clinical suspicion of PCV rather than CSC. Five study patients had detachment with associated subretinal lipid. Six of the cases
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Figure 6. ICG angiogram of a 64-year-old male that reveals a polypoidal choroidal vascular abnormality with branching vessels terminating in multiple polypoidal lesions.
eventually became associated with subretinal hemorrhage, in one instance after several weeks of detachment (Case #4); months after detachment (Cases #6, #9), and even several years after multiple, recurrent neurosensory detachments (Case #8, #12). Yet, chronic neurosensory detachments in CSC may be associated with lipid deposition as large li-
pophilic molecules accumulate intraretinally and subretinally, coincident with longevity.7,9 CNV and subretinal blood are also potential complications in CSC.7,9,10 However, lipid and bleeding are paramount features of PCV.12,15,16,20 In our cases, it was not always possible to determine whether the PCV was a primary pathogenetic factor for the macular detachment or a secondary manifestation induced by exudation or nonspecific disturbance of the RPE. Only four cases had bilateral disease (Case #4, #7, #8, and #13). One had a disciform scar; one had PCV, one had non-specific RPE changes, and one had an epiretinal membrane in the fellow eye. The patient with the disciform scar in the fellow eye most probably had PCV which evolved into a mix form of CNV. CSC has a marked tendency to be bilateral with non exudative changes present in both eyes in more than 80% of the cases in our files.7,9 It is not uncommon for PCV on the other hand to be unilateral.15,16 So, unilateral presentations should alert the clinician to the possibility of PCV in an eye suspected of having chronic CSC. Seven of the study cases had serous PEDs which are commonly seen with CSC and PCV. In some eyes, serous PEDs can be indistinguishable clinically from a small caliber polypoidal vascular abnormality. Because of their vascular nature, the polypoidal lesions tend to be reddishorange in color, but not always. When the overlying RPE is intact, it may mask the vascular appearance of the lesions, particularly if the polypoidal-CNV involves relatively small vessels. The principle way of differentiating a small serous PED from a polypoidal lesion is with ICG angiography. Knowledge of the fluorescein and ICG angiogram characteristics of a serous PED is essential in differentiating CSC from PCV. Late staining of the PED is seen with fluorescein
Figure 7. A, clinical photograph of a 60 year-old-Indian male with a 2 year history of serosanguineous detachment of the macula in the right eye. A semi-circle of lipid exudation surrounds the detachment. B, ICG angiography revealed polypoidal vascular choroidal lesions in the central macula and clustered in a curvilinear fashion in the inferior macula.
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Figure 8. A, clinical photograph of a patient with a neurosensory detachment involving the central macula. There are a few minor and non specific pigment epithelial changes. B, fluorescein angiography showed a slight degree of subretinal, indistinct leakage beneath the detachment. C, ICG angiography revealed multiple areas of choroidal staining or hyperpermeability characteristic of central serous chorioretinopathy.
angiography; whereas, the ICG angiogram shows hypofluorescence. In contrast the polypoidal lesion is hyperfluorescent with ICG angiography because of its vascular nature. There are, however, three exceptions. A very large PED in CSC, laden with fibrin exudation, may reveal a mild degree of subpigment epithelial hyperfluorescence and a notable ring of staining at its margins with ICG angiography.28,31 The fibrin has an affinity for the ICG dye and for the dye protein bio-conjugate. Another exception is the PED that overlies an area of choroidal hyperpermeability.30 This situation results in choroidal transmission of hyperfluorescence through the subpigment epithelial space, a form of pseudo-pigment epithelial fluorescence. It is important to keep in mind that a PCV lesion may exist under a PED. The portion of the PED overlying the PCV lesion will be hypofluorescent. If the PCV lesion is actually leaking, the ICG dye may extend or “pool” into the subpigment epithelial
space.20,31 Finally, ICG angiography is also of importance in differentiating PCV from CSC on the basis of multifocal areas of choroidal hyperpermeability. As mentioned above, there is a consistent finding in CSC and not in manifestations of PCV. The importance for an accurate clinical distinction between CSC and PCV is obvious. Each entity has its own independent set of demographic risk files and clinical and angiographic features. They may also differ in their natural course, visual prognosis, and response to treatment.2,3,8,9,12,20 Actually, the natural course of each disorder is not well known; nor is there a clearly established treatment based on prospective, randomized clinical trials. Yet, most retinal specialists will consider and employ laser photocoagulation treatment for CSC when there is a persistent detachment, particularly when associated with decompensating RPE, visual decline and an eccentric focal RPE leak.9,10 The assumption is
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Ophthalmology Volume 107, Number 4, April 2000 Table 1. Summary of cases
Case
Age
Sex
Race
Eye
Fellow eye
1 2 3 4 5 6 7 8 9 10 11 12 13
50 49 56 62 26 69 60 64 63 57 37 54 51
F M M F M M F M M M F F M
W A W H B H I W W W W W W
OS OS OD OD OS OS OD OD OS OS OD OS OS
n n n Scar n Prosthesis n PCV n n n n ERM
Clinical Examination
Fluorescein Angio
ICG Angio
Lipid
Blood
Protein
Staining
PED
PCV
Hyperper
PCV
X — — X — X X X — — X — —
— — — X — X X X X — — X —
— — — X X — — — — X — — —
X — — X X X X X X X X X X
— X X — X — X — X X X — —
— X X — — — — — — — — — —
— — — — — — — — — — — — —
X X X X X X X X X X X X X
A ⫽ Asian; B ⫽ Black; ERM ⫽ epiretinal membrane; F ⫽ female; fluorescein angio ⫽ fluorescein angiography; H ⫽ Hispanic; hyperper ⫽ choroidal hyperpermeability; I ⫽ Indian; ICG angio ⫽ ICG angiography; M ⫽ male; n ⫽ normal; OS ⫽ left eye; OD ⫽ right eye; PCV ⫽ polypoidal choroidal vasculopathy; PED ⫽ pigment epithelium detachment; scar ⫽ disciform scar; W ⫽ White.
that a more accelerated resolution of the neurosensory detachment is likely to preserve or restore central vision and possibly decrease the recurrence rate. Laser treatment of chronic CSC has not been generally successful.7,10 Laser photocoagulation treatment of active polypoidal lesions, accounting for serosanguineous detachments of the macula, has also been used empirically to accelerate the resolution of subfoveal blood and exudate. Such treatment is also presumptive, anecdotal and rational, yet unproven in terms of its efficacy and safety.12,16,20 Although two patients (cases #1 and #8) with chronic detachment had resolution of the detachment and improvement of vision after laser treatment, other patients (case #3 and case #4) had a favorable natural course without laser intervention. Future studies are needed to determine the exact role of laser treatment in CSC, PVC, and the peculiar variant of PCV which masquerades as chronic CSC described in this series. In summary, patients with CSC may become associated with clinical and fluorescein angiographic manifestations which are indistinguishable from PCV. In such cases, ICG angiography should be performed to establish a more definitive diagnosis, particularly in 1) patients who are generally not at risk of CSC on the basis age, sex, or race, 2) eyes with persistent detachments associated with lipid, and 3) recurrent detachments with subretinal blood. Accurate diagnosis is important to the clinician in the management of these patients.
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