Ophthalmology Volume 122, Number 7, July 2015 References 1. Varma R, Spaeth GL, Hanau C, et al. Positional changes in the vasculature of the optic disk in glaucoma. Am J Ophthalmol 1987;104:457–64. 2. Radcliffe NM, Smith SD, Syed ZA, et al. Blood vessel position shifts and glaucoma progression. Ophthalmology 2014;121: 842–8. 3. Mochizuki H, Lesley AG, Brandt JD. Shrinkage of the scleral canal during cup reversal in children. Ophthalmology 2011;118:2008–13.
Focal Choroidal Excavation in Multifocal Choroiditis and Punctate Inner Choroidopathy In 2006, Jampol et al1 described an unusual optical coherence tomography (OCT) finding that is now widely called “focal choroidal excavation (FCE).”2 Focal choroidal excavation is often associated with macular choroidal diseases, including central serous chorioretinopathy, choroidal neovascularization (CNV), and polypoidal choroidal vasculopathy.2,3 However, the origin, natural history, and clinical implications of FCE are largely unknown. Although FCE is known as a relatively stationary lesion, it has been shown recently that FCE can grow and develop de novo secondary to progression of CNV, suggesting the possibility of an acquired nature of this lesion, at least in some of the cases.3 In about 50% of the eyes with FCE, unusual hyperreflective choroidal tissue is detected on OCT, which may represent choroidal scarring.3 Multifocal choroiditis and panuveitis (MCP) and punctate inner choroidopathy (PIC) are characterized by multifocal yellow-white spots at deep retina/inner choroid layers, that evolve into atrophic scars.4 Because MCP/PIC is characterized by focal inflammation at the retinal pigment epithelium (RPE) and inner choroid, we investigated whether focal scarring changes at the outer retina/inner choroid in MCP/PIC are associated with the presence or induction of FCE. We reviewed retrospectively the medical records of 33 eyes from 21 PIC patients and 21 eyes of 15 MCP patients diagnosed at 2 tertiary medical centers between October 2008 and December 2013. Of 54 eyes with MCP/PIC, 11 eyes (20%) from 11 patients had FCE, and the clinical characteristics of those patients were evaluated. This study was approved by the institutional review board of both hospitals. We defined FCE as choroidal excavation observed on OCT without evidence of posterior staphyloma.2 The width and depth of FCEs were measured using the caliper provided by the Heidelberg Spectralis OCT software. We diagnosed PIC if eyes with typical fundus lesions showed no signs of anterior uveitis or vitritis. If eyes had a history of inflammatory cells in the anterior chamber or vitreous cavity as determined by ophthalmoscopy or spectral domain OCT, they were classified as MCP.4 We diagnosed CNV on the basis of clinical, angiographic, and OCT findings. Demography and clinical findings are shown in Table 1 (available at www.aaojournal.org). All 15 FCEs in 11 MCP/PIC eyes were classified as conforming type, showing no separated area between the photoreceptor tip and the RPE. On fundus examination, FCEs were not discernible in 5 cases (33.3%) and appeared as yellowish spots in 4 (26.7%). The remaining 6 FCEs
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were associated with CNV (40%), of which 2 FCEs seemed to newly develop from an originally nonexcavated choroid (Fig 1). Preexisting FCEs could act as platforms for developing CNV, perhaps owing to relative choroidal ischemia at the excavated area, but FCEs could also arise from CNV as shown in Figure 1.3 During a mean follow-up of 28.230.5 months, the mean width of the FCE significantly increased from 806.50512.32 mm to 916.67469.23 mm (P ¼ 0.017). The depth and depth/width ratio of FCE did not increase significantly, but the relative thickness of the choroid under the lesion compared with the unaffected adjacent choroidal thicknesses were decreased significantly (P ¼ 0.006), suggesting lesion enlargement in an anterioreposterior direction. When we compared the OCT findings of FCEs in MCP/PIC with those of 21 “idiopathic” FCEs from our previously published data,3 the inner retina was retracted toward the choroid in 6 of 15 FCEs (40%) with MCP/PIC, but was not observed in any of idiopathic FCE cases. Choroidal scarring, defined as hyperreflective choroidal tissue under the excavation on OCT3 was observed more frequently in MCP/PIC-associated FCEs (93%) than in idiopathic FCEs (57.1%; P ¼ 0.019). This hyperreflective choroidal tissue may suggest the possible involvement of choroidal scarring in the pathogenesis of FCE.3 Because MCP and PIC are characterized by focal inflammation of the RPE and inner choroid, this inflammation and subsequent scarring may act as an initiating and/or exacerbating factor for the development and/or progression of FCE. This scarring may explain why FCE was detected more frequently in MCP/PIC than in other reported choroidal diseases such as central serous chorioretinopathy or CNV.3 It could be argued that choroidal excavation associated with outer retinal/choroidal inflammation is a secondary change and may not represent the same entity as “idiopathic” FCE. Focal choroidal excavation is an OCT phenotype and there is currently no consensus on the definition of FCE. Perhaps, it would be advisable to separate FCEs into “primary” lesions without the evidence of scarring changes and “secondary” lesions associated with inflammation or CNV. Five FCEs in this study were not associated with CNV or MCP/PIC-related fundus findings. These lesions could represent “primary” FCEs. However, they may also be the consequence of subtle or subclinical episodes of MCP/PIC. Interestingly, a patient with 3 such seemingly “primary” FCEs developed active inflammation at the site of the FCE, which then developed MCP/PIC-like fundus lesions (Fig 2; available at www.aaojournal.org). Although primary FCEs may represent developmental abnormalities, we speculate that many primary or idiopathic cases may actually be secondary to asymptomatic or subclinical focal chorioretinitis or focal insults that can result in structural choroidal changes. Many investigators have hypothesized that FCE is a congenital malformation. Interestingly, a recent study suggested an association between FCE and Epstein-Barr virus infection,5 which is a well-known cause of intrauterine chorioretinitis. In conclusion, FCE was frequently detected in MCP/PIC eyes. Focal choroidal excavations were associated with MCP/PIC lesions, or CNV, or independent of other chorioretinal abnormalities. Atrophic scarring changes involving the outer retina/inner choroid appear to be involved in the pathogenesis of these excavated lesions, which showed gradual progression over time.
Reports
Figure 1. A 21-year-old woman with punctate inner choroidopathy (PIC) and choroidal neovascularization (CNV; patient 3). A, Fundus photograph reveals a subfoveal grey-yellow lesion. B, C, Serial fluorescein angiography (FA) reveals active fluorescein leakages, suggesting CNV development. D, Spectral-domain optical coherence tomography (SD OCT) at the time of A reveals disruption of retinal pigment epithelium (RPE) and subretinal fluid. E, SD OCT scan 1 month after intravitreal bevacizumab injection reveals the resolution of CNV. Subfoveal choroidal thickness has decreased compared with D. F, After 12 months, a SD OCT scan reveals choroidal excavation with increased choroid hyperreflectivity, decreased choroidal thickness, and retraction of inner retina.
HYESUN KIM, MD1 SE JOON WOO, MD2 YONG-KYU KIM, MD2 SUNG CHUL LEE, MD1 CHRISTOPHER SEUNGKYU LEE, MD1 1
The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea; 2Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Correspondence: Christopher Seungkyu Lee, MD, Department of Ophthalmology, Yonsei University College of Medicine, Sodaemungu Shinchondong 134, Seoul 120-752, Korea. E-mail: [email protected].
References 1. Jampol LM, Shankle J, Schroeder R, et al. Diagnostic and therapeutic challenges. Retina 2006;26:1072–6. 2. Margolis R, Mukkamala SK, Jampol LM, et al. The expanded spectrum of focal choroidal excavation. Arch Ophthalmol 2011;129:1320–5. 3. Lee CS, Woo SJ, Kim YK, et al. Clinical and spectral-domain optical coherence tomography findings in patients with focal choroidal excavation. Ophthalmology 2014;121:1029–35. 4. Spaide RF, Goldberg N, Freund KB. Redefining multifocal choroiditis and panuveitis and punctate inner choroidopathy through multimodal imaging. Retina 2013;33:1315–24.
5. Savastano MC, Rispoli M, Di Antonio L, et al. Observed positive correlation between Epstein-Barr virus infection and focal choroidal excavation. Int Ophthalmol 2014;34: 927–32.
Optical Coherence Tomography of Chorioretinopathy Caused by Mucopolysaccharidoses Ocular changes in some types of the mucopolysaccharidoses (MPS) include corneal clouding, glaucoma, pigmentary retinopathy, optic disc edema, and optic atrophy.1,2 Pigmentary retinopathy has been reported in MPS I (Hurler disease), MPS I-S (Scheie syndrome), MPS I-H/S (Hurler/Scheie), MPS II (Hunter disease), MPS III (Sanfilippo syndrome), and MPS IV A (Morquio A syndrome).1,2 Clinical signs of retinopathy include atrophy of the retinal pigment epithelium (RPE), arteriolar narrowing, and later bone spicules. The electroretinographic abnormality is a pattern of rodecone dystrophy.2 Histopathologic examinations have demonstrated widespread loss of RPE and photoreceptors.3 However, there have been no histopathologic descriptions of the retinas in mild forms of MPS. Using optical coherence tomography (OCT), we have attempted to provide a detailed morphologic description of the retina and the choroid in cases with MPS. Institutional review board approval was obtained. A total of 42 eyes of 21 consecutive patients with MPS were enrolled in this study, including 3 patients with MPS I (2 male, 1 female), 5 patients with MPS II (all male), 8 patients with MPS IV A (2 male, 6 female), and 5 patients with MPS VI (3 male, 2 female). Patients
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Focal Choroidal Excavation in Multifocal Choroiditis and Punctate Inner Choroidopathy In 2006, Jampol et al1 described an unusual optical coherence tomography (OCT) finding that is now widely called “focal choroidal excavation (FCE).”2 Focal choroidal excavation is often associated with macular choroidal diseases, including central serous chorioretinopathy, choroidal neovascularization (CNV), and polypoidal choroidal vasculopathy.2,3 However, the origin, natural history, and clinical implications of FCE are largely unknown. Although FCE is known as a relatively stationary lesion, it has been shown recently that FCE can grow and develop de novo secondary to progression of CNV, suggesting the possibility of an acquired nature of this lesion, at least in some of the cases.3 In about 50% of the eyes with FCE, unusual hyperreflective choroidal tissue is detected on OCT, which may represent choroidal scarring.3 Multifocal choroiditis and panuveitis (MCP) and punctate inner choroidopathy (PIC) are characterized by multifocal yellow-white spots at deep retina/inner choroid layers, that evolve into atrophic scars.4 Because MCP/PIC is characterized by focal inflammation at the retinal pigment epithelium (RPE) and inner choroid, we investigated whether focal scarring changes at the outer retina/inner choroid in MCP/PIC are associated with the presence or induction of FCE. We reviewed retrospectively the medical records of 33 eyes from 21 PIC patients and 21 eyes of 15 MCP patients diagnosed at 2 tertiary medical centers between October 2008 and December 2013. Of 54 eyes with MCP/PIC, 11 eyes (20%) from 11 patients had FCE, and the clinical characteristics of those patients were evaluated. This study was approved by the institutional review board of both hospitals. We defined FCE as choroidal excavation observed on OCT without evidence of posterior staphyloma.2 The width and depth of FCEs were measured using the caliper provided by the Heidelberg Spectralis OCT software. We diagnosed PIC if eyes with typical fundus lesions showed no signs of anterior uveitis or vitritis. If eyes had a history of inflammatory cells in the anterior chamber or vitreous cavity as determined by ophthalmoscopy or spectral domain OCT, they were classified as MCP.4 We diagnosed CNV on the basis of clinical, angiographic, and OCT findings. Demography and clinical findings are shown in Table 1 (available at www.aaojournal.org). All 15 FCEs in 11 MCP/PIC eyes were classified as conforming type, showing no separated area between the photoreceptor tip and the RPE. On fundus examination, FCEs were not discernible in 5 cases (33.3%) and appeared as yellowish spots in 4 (26.7%). The remaining 6 FCEs
1534
were associated with CNV (40%), of which 2 FCEs seemed to newly develop from an originally nonexcavated choroid (Fig 1). Preexisting FCEs could act as platforms for developing CNV, perhaps owing to relative choroidal ischemia at the excavated area, but FCEs could also arise from CNV as shown in Figure 1.3 During a mean follow-up of 28.230.5 months, the mean width of the FCE significantly increased from 806.50512.32 mm to 916.67469.23 mm (P ¼ 0.017). The depth and depth/width ratio of FCE did not increase significantly, but the relative thickness of the choroid under the lesion compared with the unaffected adjacent choroidal thicknesses were decreased significantly (P ¼ 0.006), suggesting lesion enlargement in an anterioreposterior direction. When we compared the OCT findings of FCEs in MCP/PIC with those of 21 “idiopathic” FCEs from our previously published data,3 the inner retina was retracted toward the choroid in 6 of 15 FCEs (40%) with MCP/PIC, but was not observed in any of idiopathic FCE cases. Choroidal scarring, defined as hyperreflective choroidal tissue under the excavation on OCT3 was observed more frequently in MCP/PIC-associated FCEs (93%) than in idiopathic FCEs (57.1%; P ¼ 0.019). This hyperreflective choroidal tissue may suggest the possible involvement of choroidal scarring in the pathogenesis of FCE.3 Because MCP and PIC are characterized by focal inflammation of the RPE and inner choroid, this inflammation and subsequent scarring may act as an initiating and/or exacerbating factor for the development and/or progression of FCE. This scarring may explain why FCE was detected more frequently in MCP/PIC than in other reported choroidal diseases such as central serous chorioretinopathy or CNV.3 It could be argued that choroidal excavation associated with outer retinal/choroidal inflammation is a secondary change and may not represent the same entity as “idiopathic” FCE. Focal choroidal excavation is an OCT phenotype and there is currently no consensus on the definition of FCE. Perhaps, it would be advisable to separate FCEs into “primary” lesions without the evidence of scarring changes and “secondary” lesions associated with inflammation or CNV. Five FCEs in this study were not associated with CNV or MCP/PIC-related fundus findings. These lesions could represent “primary” FCEs. However, they may also be the consequence of subtle or subclinical episodes of MCP/PIC. Interestingly, a patient with 3 such seemingly “primary” FCEs developed active inflammation at the site of the FCE, which then developed MCP/PIC-like fundus lesions (Fig 2; available at www.aaojournal.org). Although primary FCEs may represent developmental abnormalities, we speculate that many primary or idiopathic cases may actually be secondary to asymptomatic or subclinical focal chorioretinitis or focal insults that can result in structural choroidal changes. Many investigators have hypothesized that FCE is a congenital malformation. Interestingly, a recent study suggested an association between FCE and Epstein-Barr virus infection,5 which is a well-known cause of intrauterine chorioretinitis. In conclusion, FCE was frequently detected in MCP/PIC eyes. Focal choroidal excavations were associated with MCP/PIC lesions, or CNV, or independent of other chorioretinal abnormalities. Atrophic scarring changes involving the outer retina/inner choroid appear to be involved in the pathogenesis of these excavated lesions, which showed gradual progression over time.
Reports
Figure 1. A 21-year-old woman with punctate inner choroidopathy (PIC) and choroidal neovascularization (CNV; patient 3). A, Fundus photograph reveals a subfoveal grey-yellow lesion. B, C, Serial fluorescein angiography (FA) reveals active fluorescein leakages, suggesting CNV development. D, Spectral-domain optical coherence tomography (SD OCT) at the time of A reveals disruption of retinal pigment epithelium (RPE) and subretinal fluid. E, SD OCT scan 1 month after intravitreal bevacizumab injection reveals the resolution of CNV. Subfoveal choroidal thickness has decreased compared with D. F, After 12 months, a SD OCT scan reveals choroidal excavation with increased choroid hyperreflectivity, decreased choroidal thickness, and retraction of inner retina.
HYESUN KIM, MD1 SE JOON WOO, MD2 YONG-KYU KIM, MD2 SUNG CHUL LEE, MD1 CHRISTOPHER SEUNGKYU LEE, MD1 1
The Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea; 2Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Correspondence: Christopher Seungkyu Lee, MD, Department of Ophthalmology, Yonsei University College of Medicine, Sodaemungu Shinchondong 134, Seoul 120-752, Korea. E-mail: [email protected].
References 1. Jampol LM, Shankle J, Schroeder R, et al. Diagnostic and therapeutic challenges. Retina 2006;26:1072–6. 2. Margolis R, Mukkamala SK, Jampol LM, et al. The expanded spectrum of focal choroidal excavation. Arch Ophthalmol 2011;129:1320–5. 3. Lee CS, Woo SJ, Kim YK, et al. Clinical and spectral-domain optical coherence tomography findings in patients with focal choroidal excavation. Ophthalmology 2014;121:1029–35. 4. Spaide RF, Goldberg N, Freund KB. Redefining multifocal choroiditis and panuveitis and punctate inner choroidopathy through multimodal imaging. Retina 2013;33:1315–24.
5. Savastano MC, Rispoli M, Di Antonio L, et al. Observed positive correlation between Epstein-Barr virus infection and focal choroidal excavation. Int Ophthalmol 2014;34: 927–32.
Optical Coherence Tomography of Chorioretinopathy Caused by Mucopolysaccharidoses Ocular changes in some types of the mucopolysaccharidoses (MPS) include corneal clouding, glaucoma, pigmentary retinopathy, optic disc edema, and optic atrophy.1,2 Pigmentary retinopathy has been reported in MPS I (Hurler disease), MPS I-S (Scheie syndrome), MPS I-H/S (Hurler/Scheie), MPS II (Hunter disease), MPS III (Sanfilippo syndrome), and MPS IV A (Morquio A syndrome).1,2 Clinical signs of retinopathy include atrophy of the retinal pigment epithelium (RPE), arteriolar narrowing, and later bone spicules. The electroretinographic abnormality is a pattern of rodecone dystrophy.2 Histopathologic examinations have demonstrated widespread loss of RPE and photoreceptors.3 However, there have been no histopathologic descriptions of the retinas in mild forms of MPS. Using optical coherence tomography (OCT), we have attempted to provide a detailed morphologic description of the retina and the choroid in cases with MPS. Institutional review board approval was obtained. A total of 42 eyes of 21 consecutive patients with MPS were enrolled in this study, including 3 patients with MPS I (2 male, 1 female), 5 patients with MPS II (all male), 8 patients with MPS IV A (2 male, 6 female), and 5 patients with MPS VI (3 male, 2 female). Patients
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