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Polypoidal Choroidal Vasculopathy in Tilted Disk Syndrome and High Myopia With Staphyloma
Polypoidal Choroidal Vasculopathy in Tilted Disk Syndrome and High Myopia With Staphyloma MARTINE MAUGET-FAŸSSE, MD, PIERRE-LOÏC CORNUT, MD, MADDALENA QUARANTA EL-MAFTOUHI, MD, AND ANITA LEYS, MD
● PURPOSE:
To describe polypoidal choroidal vasculopathy as a complication of tilted disk syndrome and high myopia with staphyloma. ● DESIGN: Retrospective interventional case series. ● METHODS: This report was a multicenter evaluation of six patients (eight eyes) with tilted disk syndrome or high myopia that was complicated by posterior staphyloma. Complete ophthalmic examination that included fluorescein angiography, optical coherence tomography (OCT), and indocyanine green angiography (ICG-A) was performed in all patients. ● RESULTS: All patients had macular abnormalities and visual loss. Fundus examination and fluorescein angiography showed typical features of tilted disk syndrome (five patients; six eyes) or high myopia (one patient; two eyes) with staphyloma that was associated with polypoidal choroidal vasculopathy. OCT and ICG-A confirmed the presence of polypoidal dilations in the choroid. Seven eyes were treated with laser photocoagulation or verteporfin-photodynamic therapy (V-PDT), although one eye did not require treatment. Visual acuity at the final visit had improved in three eyes, deteriorated in three eyes, and remained unchanged in two eyes. ● CONCLUSION: Polypoidal choroidal vasculopathy is a potential cause of visual loss in tilted disk syndrome and high myopia. We postulate that choroidal abnormalities at the border of staphylomas induce blood-flow disturbances that are similar to those disturbances that are observed in chronic central serous chorioretinopathy, which is another condition that occasionally is associated with polypoidal choroidal vasculopathy. The pathogenesis remains unclear, and further study is required to better understand the formation of choroidal polypoidal dilations in these conAccepted for publication Jun 21, 2006. From the Rabelais Ophthalmologic Center, Lyon, France (M.M.-F., M.Q.-E.M.); Department of Ophthalmology, Lyon E. Herriot University Hospital, Lyon, France (P.-L.C.); Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium (A.L.). Inquiries to Martine Mauget-Fay¨sse, MD, Rabelais Ophthalmologic Center, 12–14 rue Rabelais, 69003 Lyon, France; e-mail: centrerabelais@ wanadoo.fr
970
©
2006 BY
ditions. (Am J Ophthalmol 2006;142:970 –975. © 2006 by Elsevier Inc. All rights reserved.)
T
ILTED DISK SYNDROME IS ONE OF THE OCULAR MAL-
formations that is associated with malclosure of the embryonic optic fissure.1 Tilted optic disks are relatively common and occur in 1.6% of the optic nerves. This anomaly results from optic disk dysversion and/or torsion (pseudorotation of the superior pole of the optic disk, angulation of the optic cup axis inferonasally, and elevation of the superotemporal neuroretinal rim). The disk anomaly is only one component of tilted disk syndrome and is accompanied classically by the following signs: astigmatism (93%), myopia (66%), situs inversus of the retinal vessels (70%), peripapillary atrophy (65%), inferonasal chorioretinal thinning (5%), posterior staphyloma (18%), and visual field defects (19%).2 Posterior staphyloma is a feature common to both high myopia and tilted disk syndrome. Occasionally, patients with tilted disk syndrome or high myopia have visual loss that results from choroidal neovascularization or neurosensory macular detachment that mimics central serous chorioretinopathy.3–5 Interestingly, especially in patients with tilted disk syndrome, these lesions usually are located at the junction between the altered and normal chorioretina (at the edge of the staphyloma), which suggests a relationship between localized retinal pigment epithelium dysfunction and choroidal perfusion anomalies.3 Polypoidal choroidal vasculopathy is characterized by the presence of dilated, choroidal vascular channels of a branching abnormal vascular network that ended in orange, bulging, polyp-like dilations that elevate the retinal pigment epithelium. Polypoidal dilations are globular, well-defined, hyperfluorescent, round lesions that usually are seen better at the edge of an interconnecting vascular network in the venous phase of indocyanine green angiography (ICG-A).6 These lesions usually occur in the peripapillary, macular, and peripheral retinal regions. Associated features are recurrent hemorrhagic detachments of the retinal pigment
ELSEVIER INC. ALL
RIGHTS RESERVED.
0002-9394/06/$32.00 doi:10.1016/j.ajo.2006.06.063
12 20/50 Yes OS
Female 63 HMWS 6
PCV
IN
TDS ⫽ tilted disk syndrome; HMWS ⫽ high myopia with staphyloma; OD ⫽ right; OS ⫽ left.
20/25
20/200 Count fingers 20/80 20/25 20/60 Count fingers 20/30 20/25 No Yes Yes Yes 64 66 TDS TDS 4 5
Male Female
OD OD OS OD
–0.5 (–2 * 80°) –10 Before pseudophakia –10 Before pseudophakia –8.5 (–3 * 10°) Before pseudophakia –10.75 (–3.75 * 180°) Before pseudophakia
20/40 20/50 No 63 TDS 3
Female
OD
–9.25 (–1.5 * 0°)
20/60 20/80 No 74 TDS 2
Female
OS
–4 (–0.5 * 85°)
Laser (n ⫽ 3)
(n ⫽ 1)
63 72 30 12
17 with
5 with
5 No 74 TDS 1
Male
OD
–3.5 (–3 * 0°)
20/100
20/50
Photodynamic therapy verteporfin (n ⫽ 2) Photodynamic therapy verteporfin (n ⫽ 2) Photodynamic therapy verteporfin (n ⫽ 5) Laser (n ⫽ 3) None Photodynamic therapy Laser (n ⫽ 3)
with
Follow-Up (mo) Treatment Final Visual Acuity Initial Visual Acuity Refractive Error Pseudophakia Eye Gender Age (y) TDS and HMWS Patient
TABLE. Clinical Characteristics of Patients With Polypoidal Choroidal Vasculopathy in Tilted Disk Syndrome (Case 1 to 5) and High Myopia With Staphyloma (Case 6)
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FIGURE 1. Case 1, Top left: Fluorescein angiography shows area of leakage (black arrow) that was associated with a more hyperfluorescent spot at the site of the polypoidal dilation (white arrow). Top right: Indocyanine green angiogram (ICG-A) with polypoidal choroidal dilation (white arrow), atypical choroidal drainage venous routes and venous congestion with irregular and tortuous or possibly occluded choroidal veins. Bottom: Optical coherence tomography (OCT) scans (gray scale) shows circumscribed elevations with signs of rupture of the retinal pigment epithelium/choriocapillaris complex (white arrow) and a thin serous retinal detachment (open arrow).
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FIGURE 2. Case 2, Left: Fluorescein angiography shows area of leakage (black arrow) that was associated with a more hyperfluorescent spot at the site of the polypoidal dilation (white arrow). Right: Indocyanine green angiogram (ICG-A) with polypoidal choroidal dilation (white arrow), atypical choroidal drainage venous routes and venous congestion with irregular and tortuous or possibly occluded choroidal veins. Note the similarities between cases 1 and 2.
epithelium and serohemorrhagic retinal detachments with relatively minimal fibrous scarring. We discuss the characteristics of polypoidal choroidal vasculopathy in a consecutive case series of six patients (eight eyes) with tilted disk syndrome (TDS) or high myopia with staphyloma (HMWS). To the best of our AND
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FIGURE 3. Case 3, Left: Fluorescein angiography shows a large area of leakage associated with sub retinal hemorrhages and a temporal pigment epithelial detachment (white arrow). Right: Indocyanine green angiogram (ICG-A) shows polypoidal choroidal dilations (white circle).
FIGURE 4. Case 4, Left: Fluorescein angiography shows a large area of leakage. Right: Indocyanine green angiogram (ICG-A) shows polypoidal choroidal dilations (white circle) on the way of the superotemporal venous drainage.
knowledge, this is the first report of polypoidal choroidal vasculopathy complicating eyes with TDS or HMWS.
were Caucasian. TDS with polypoidal choroidal vasculopathy was present in five patients (six eyes); HMWS and polypoidal choroidal vasculopathy was present in one patient (two eyes). The mean refractive error of the affected eyes with TDS was ⫺6.8 ⫾ 3.7 diopters (range, ⫺1.5 to ⫺10 diopters). The TDS or HMWS was bilateral in all the study patients. One patient with TDS and the only patient with HMWS had bilateral polypoidal choroidal vasculopathy; this condition was unilateral in all the other patients. All the study patients had macular abnormalities and visual loss. The visual acuity at evaluation varied from “counting fingers” to 20/25. Fundus biomicroscopy (Figure 5) showed subretinal hemorrhages in all eyes. Five eyes also had lipoid exudates (cases 2, 3, 4, 5 OD and 6 OS). All the study eyes had a serous retinal detachment, with three eyes having combined serous pigment epithelial detachment (PED; Figures 3, 5, and 8). Polypoidal choroidal vasculopathy was discovered by fluorescein angiography in the left eye of case 6 (Figure 8). Fluorescein angiography highlighted the presence of hyperfluorescent zones, with pinpoints that correspond to areas of leakage and more hyperfluorescent spots at the site of the polypoidal dilations in all the study patients (Figures 1 to 8). ICG-A, which allowed the analysis of the choroidal vasculature, showed choroidal venous abnormalities with dilated and irregular drainage veins in the proximity of choroidal polypoidal dilations (Figures 1 to 8). These typically hyperfluorescent polypoidal abnormalities were better seen in the venous phase of ICG-A. All the polypoidal dilations were located at the junction between the staphyloma and the normal retina. The direction of the drainage of the veins with polypoidal dilations at inclusion was toward the superotemporal vortex vein. A feeder vessel was not demonstrated clearly in any study patient. The abnormal vascular network was well-defined as a plaque in the late phase. In one patient, a new drainage route appeared with a vaginal vein (Figure 5). On OCT scans (Figure 1), polypoidal dilations were identified as circumscribed elevations of the retinal pigment epithe-
METHODS THIS STUDY IS A RETROSPECTIVE, MULTICENTER, INTER-
ventional case series that was performed in compliance with the Declaration of Helsinki. All the study patients (six patients, eight eyes) were evaluated in the authors’ affiliated institutions between 1999 and 2006 with a diagnosis of TDS or HMWS and complicated with polypoidal choroidal vasculopathy. At each visit, a complete examination of both eyes was performed that included best-corrected visual acuity examination with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, slit-lamp biomicroscopy, fluorescein angiography with the Topcon 50IA (Topcon, Inc, Paramus, New Jersey, USA), Topcon 50IX (Topcon, Inc, Paramus, New Jersey, USA), or OIS fundus cameras (Ophthalmic Imaging System, Sacramento, California, USA) and ICG-A with the Topcon 50IA or HRA 2 Heidelberg fundus camera (Heidelberg Engineering, GmbH, Dossenheim, Germany). Optical coherence tomography (OCT) scans (Zeiss Humphrey, Oberkochen, Germany) were performed after ICG-A over the area with choroidal polypoidal dilations and across the fovea (6 mm vertical and 6 mm perpendicular). The patients were treated, if required, with laser photocoagulation or verteporfin-photodynamic therapy (V-PDT). The main outcome measures were final visual acuity and angiographic and OCT scan features.
RESULTS THE RESULTS ARE SUMMARIZED IN THE TABLE; THE ANGIO-
graphic and OCT features of the study patients are shown in Figures 1 to 8. The mean age of the patients was 67.3 ⫾ 5.3 (SD) years (range, 63 to 74 years). There were two male patients and four female patients. All the patients 972
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FIGURE 5. Case 5, right eye. Top left: Fundus photograph at baseline shows a large subretinal hemorrhage, small lipoid exudates, and the presence of a temporal pigment epithelial detachment. Top right: Fluorescein angiography shows a hyperfluorescent leaking area in the maculopapillary region and confirms the pigment epithelial detachment seen on fundus photography (white arrow). Bottom: Spontaneous evolution of the choroidal venous blood flow is documented on indocyanine green angiogram (ICG-A) images. Initially, (Bottom left) a large pigment epithelial detachment is seen with a vascular network and numerous polypoidal dilations in the notch; afferent and efferent choroidal vessels are seen in the maculopapillary region. One year later (Middle bottom), the polypoidal dilations are larger and stain heavily. Another year later (Bottom right), the pigment epithelial detachment and polypoidal dilations have disappeared; venovenous anastomoses (circle) have developed that connect the inferotemporal area to a vaginal vein (white arrows) with progressive dilation of the new drainage route. This newly formed drainage route appears to have developed to reduce the previous venous congestion.
FIGURE 6. Case 5, left eye. Left: Fluorescein angiography shows a large area of leakage with pinpoints. Right: Indocyanine green angiogram (ICG-A) shows numerous small polypoidal choroidal dilations (white circle).
lium/choriocapillaris complex with, in the active phase, an optically mildly reflective heterogeneous filling that was associated with serous retinal detachment. At inclusion, OCT scans confirmed that three eyes had PEDs, although all eyes had serous retinal detachments and retinal thickening (Figure 1). Treatment was given to seven eyes, with laser photocoagulation in three eyes and V-PDT in four eyes. One eye with very poor vision at evaluation did not receive treatment (case 5 OD). After V-PDT, venous drainage improved with reduction in venous swelling and normalization of venous calibers; the choroid appeared to have remodeled. Visual acuity at the final visit had increased slightly in three eyes, decreased VOL. 142, NO. 6
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FIGURE 7. Polypoidal choroidal vasculopathy in high myopia with staphyloma in case 6, right eye. Left: Fluorescein angiography shows a small area of leakage with pinpoints next to linear changes of the retinal pigment epithelium temporal to the macula. Right: Indocyanine green angiogram (ICG-A) shows a small cluster of numerous polypoidal choroidal dilations.
slightly in three eyes, and was unchanged at 20/25 in one eye. In the only untreated eye, visual acuity remained at counting fingers. Of the four eyes with a posttreatment follow-up period of more than one year, only one eye had improved visual acuity.
DISCUSSION VISUAL LOSS BECAUSE OF MACULOPATHY IS NOT UNCOM-
mon in eyes with TDS or HMWS. We report, for the first AND
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FIGURE 8. Polypoidal choroidal vasculopathy in high myopia with staphyloma in case 6, left eye. Left: Fluorescein angiography shows numerous small polypoidal dilations (black arrows) that are associated with a pigment epithelial detachment (white arrow) in the early phase. Middle: In the later phases, progressive pooling of dye is noted in the polypoidal dilations (black arrow) and under the pigment epithelial detachment (white arrow). Moreover, intense focal subretinal leakage (open arrow) that is similar to central serous chorioretinopathy is noted at the nasal border of the pigment epithelial detachment; pinpoints are seen in a larger area. Right: Indocyanine green angiogram (ICG-A) shows numerous large polypoidal dilations that mostly are located close to the pigment epithelial detachment (black arrow) and an interconnecting network of vessels that correspond to the pinpoint lesions that are seen on the fluorescein angiography (white circle).
time, polypoidal choroidal vasculopathy as a complication of TDS or HMWS as another cause of visual loss in these patients. TDS usually is associated with low myopia.1 In this syndrome, macular pigmentary changes are observed in 11% of the patients, and macular complications are more frequent and severe in eyes with a higher degree of refractive error.7 In our report, patients with tilted disk had a mean refractive error of ⫺6.8 diopters. Pigmentary change of the retinal pigment epithelium at the crest of the staphyloma with areas of choroidal atrophy is a characteristic feature of both HMWS and TDS. Choroidal neovascularization usually arises in eyes with retinal pigment epithelium changes, in breaks in Bruch’s membrane, or in atrophic lesions.3,8 Vision loss in the fourth decade of life or later in TDS or in HMWS may be due to serous macular detachment and subretinal leakage that mimics central serous chorioretinopathy.9 The area of leakage is a site of retinal pigment epithelium dysfunction,4 which corresponds to the temporal margin of the inferonasal staphyloma in TDS and to the border of the staphyloma in patients with HMWS. Interestingly, polypoidal choroidal vasculopathy can also occur along with diffuse disturbances of the retinal pigment epithelium, which evokes the diagnosis of atypical central serous retinopathy or diffuse retinal epitheliopathy.10 In view of these observations, it is not surprising that, in TDS or HMWS, localized retinal pigment epithelium disturbances can have polypoidal choroidal vasculopathy. We suggest that polypoidal choroidal vasculopathy can result from different triggers: a vasogenic origin as in central serous chorioretinopathy, a dysplastic origin in TDS,9 and a degenerative origin in high myopia. ICG-A has provided evidence of abnormal choriocapillary blood flow in central serous chorioretinopathy. We did not observe, in our patients, any diffuse signs of hyperpermeability that are similar to those found in chronic central serous chorioretinopathy. However, choroidal dilations that are associated with PEDs, a characteristic feature of 974
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central serous chorioretinopathy, were detected in three of our patients with TDS/HMWS. Our patients of TDS/ HMWS that was complicated by polypoidal choroidal vasculopathy were different from classic idiopathic polypoidal choroidal vasculopathy. The abnormal vascular network was much less visible in the early phase of ICG-A and was more defined in the late phase of ICG-A as a plaque in all eyes. We observed angiographic similarities in our study patients (Figures 1 to 8). First, polypoidal choroidal vasculopathy always was located at the border between the hypoplastic and normal choroid at the temporal crest of the inferonasal posterior staphyloma. The hypovascularized choriocapillaries in this area of the staphyloma may have induced hypoxia that was followed by choroidal neovascularization. The difference of curvature in the area of the staphyloma may also cause blood flow disturbances that are similar to that seen in arteriovenous crossings that give rise to hypoxia and neovascularization and/or inducement of venous shunts and vascular dilations. Second, the choroidal veins in the area of polypoidal formations were dilated and irregular in all our patients, sometimes appearing similar to a process of choroidal phlebitis with slowed blood flow because of the anatomic impairment. The dilation of the choroidal veins could also be a compensatory vasodilation reflex to slow down the blood stream and protect the retina against ischemia.11 Giuffre7 reported that in patients with tilted disk syndrome, choroidal neovascularization developed in the inferotemporal edge of the staphyloma in areas with marked alterations of the retinal pigment epithelium and the frequent presence of vaginal veins (veins that drain in veins of the sheaths of the optic nerve rather than in the vortex veins). However, these vaginal veins probably were observed more easily because of the depigmentation of the retinal pigment epithelium. In one of our patients (Figure 5), a vaginal vein developed as if the previous superior drainage to the vortex vein was not effective any more. The development of new OF
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choroidal venous drainage routes that connect the sector of an occluded vortex vein to that of the intact vortex vein area with venovenous anastomoses is well-known.12,13 The choroidal venous flow alterations that are suspected on angiography must be confirmed by hemodynamic measurements. In a recent publication concerning tilted disk syndrome, ocular hemodynamic measurements that were determined by color Doppler ultrasonography were not altered in the ophthalmic artery, central retinal artery, central retinal vein, and posterior ciliary arteries. However, it is not possible to detect localized venous choroidal disturbances with color Doppler ultrasonography.14 More sophisticated techniques such as laser Doppler flowmetry might need to be used to characterize adequately the alterations in choroidal venous flow that are suspected on angiography. Our observations show that polypoidal choroidopathy is a sight threatening complication in eyes with TDS or high myopia with posterior staphyloma. Treatment can be considered in these patients either with laser coagulation or V-PDT. Although we obtained short-term favorable results after treatment and did not note adverse events, the longterm results are unknown, and there is a potential risk of late visual loss because of progressive atrophy of the scars in these myopic eyes.3 The eyes that were treated with V-PDT demonstrated significant improvement in venous drainage and calibers. The choroid appeared to have remodeled in these patients, which was consistent with the observations of Chan and associates15 after V-PDT in central serous chorioretinopathy. Chan and associates described the potential of V-PDT to narrow dilated choroidal vessels and to decrease choroidal permeability after V-PDT. In summary, we observed an abnormal vascular network with polypoidal formation in all our patients in the area between the hypoplastic and normal choroids: at the temporal crest of the inferonasal staphyloma in TDS or at the border of the posterior staphyloma in HMWS. Abnormal dilated and irregular choroidal veins, which are identical to what is frequently seen in diffuse retinal epitheliopathy or central serous chorioretinopathy, consistently were present close to the polypoidal dilations. However, the pathogenesis remains unclear, and further study is required to better understand the formation of choroidal polypoidal dilations in these conditions.
1. Apple DJ, Rabb MF, Walsh PM. Congenital anomalies of the optic disc. Surv Ophthalmol 1982;27:3– 41. 2. Vongphanit J, Mitchell P, Wang JJ. Population prevalence of tilted optic disc and the relationship of this sign to refractive error. Am J Ophthalmol 2002;133:679 – 685. 3. Leys AM, Cohen SY. Subretinal leakage in myopic eyes with a posterior staphyloma or tilted disk syndrome. Retina 2002;22: 659 – 665. 4. Theodossiadis PG, Grigoropoulos V, Emfietzoglou J, Theodossiadis GP. Optical coherence tomography study of tilted optic disk associated with macular detachment. Graefes Arch Clin Exp Ophthalmol 2006;244:122–124. 5. Stur M. Congenital tilted disk syndrome associated with parafoveal subretinal neovascularization. Am J Ophthalmol 1988;105:98 –99. 6. Ciardella AP, Donsoff IM, Huang SJ, et al. Polypoidal choroidal vasculopathy. Surv Ophthalmol 2004;49:25–37. 7. Giuffre G. Chorioretinal degenerative changes in the tilted disc syndrome. Int Ophthalmol 1991;15:1–7. 8. Quaranta M, Brindeau C, Coscas G, Soubrane G. Multiple choroidal neovascularizations at the border of a myopic posterior macular staphyloma. Graefes Arch Clin Exp Ophthalmol 2000;238:101–103. 9. Cohen SY, Quentel G, Guiberteau B, et al. Macular serous retinal detachment caused by subretinal leakage in tilted disc syndrome. Ophthalmology 1998;105:1831–1834. 10. Yannuzzi LA, Freund KB, Goldbaum M, et al. Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy. Ophthalmology 2000;107:767–777. 11. Hayreh SS, Chopdar A. Occlusion of the posterior ciliary artery: V, protective influence of simultaneous vortex vein occlusion. Arch Ophthalmol 1982;100:1481–1491. 12. Takahashi K, Kishi S. Remodeling of choroidal venous drainage after vortex vein occlusion following scleral buckling for retinal detachment. Am J Ophthalmol 2000;129: 191–198. 13. Hayreh SS, Baines JA. Occlusion of the vortex veins: an experimental study. Br J Ophthalmol 1973;57:217–238. 14. Tatlipinar S, Yagci B, Yaylali V, et al. The effect of tilted disc syndrome on ocular hemodynamic measurements. NeuroOphthalmology 2005;29:49 –52. 15. Chan WM, Lam DS, Lai TY, et al. Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level. Br J Ophthalmol 2003;87:1453–1458.
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REFERENCES
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Biosketch Martine Mauget-Faÿsse, MD, received her medical degree from Lyon University (France) and completed a post-doctoral training for retinal diseases at the Creteil Hospital. She was a consultant for retinal diseases at Bellevue Hospital in Saint-Etienne and Herriot Hospital in Lyon, France. Dr Mauget-Faÿsse has had an exclusive private practice since 2002. Her clinical expertise is in the diagnosis and management of retinal diseases, particularly in age-related macular degeneration and central serous chorioretinopathy. Dr Mauget-Faÿsse teaches low-vision and retinal diseases in Lyon University.
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Biosketch Pierre-Loïc Cornut, MD, is a graduate of Lyon University (France) and actually completed his internship at the Herriot Hospital. His area of research interest is the physiology of photoreception and the characterization of retinal mechanisms underlying the non-image-forming responses involving ganglion cells containing Melanopsin (Neurosciences Master, 2006). Dr Cornut is certified by the European Board of Ophthalmology, and is a member of the French Society of Ophthalmology and the Association for Research in Vision and Ophthalmology.
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● PURPOSE:
To describe polypoidal choroidal vasculopathy as a complication of tilted disk syndrome and high myopia with staphyloma. ● DESIGN: Retrospective interventional case series. ● METHODS: This report was a multicenter evaluation of six patients (eight eyes) with tilted disk syndrome or high myopia that was complicated by posterior staphyloma. Complete ophthalmic examination that included fluorescein angiography, optical coherence tomography (OCT), and indocyanine green angiography (ICG-A) was performed in all patients. ● RESULTS: All patients had macular abnormalities and visual loss. Fundus examination and fluorescein angiography showed typical features of tilted disk syndrome (five patients; six eyes) or high myopia (one patient; two eyes) with staphyloma that was associated with polypoidal choroidal vasculopathy. OCT and ICG-A confirmed the presence of polypoidal dilations in the choroid. Seven eyes were treated with laser photocoagulation or verteporfin-photodynamic therapy (V-PDT), although one eye did not require treatment. Visual acuity at the final visit had improved in three eyes, deteriorated in three eyes, and remained unchanged in two eyes. ● CONCLUSION: Polypoidal choroidal vasculopathy is a potential cause of visual loss in tilted disk syndrome and high myopia. We postulate that choroidal abnormalities at the border of staphylomas induce blood-flow disturbances that are similar to those disturbances that are observed in chronic central serous chorioretinopathy, which is another condition that occasionally is associated with polypoidal choroidal vasculopathy. The pathogenesis remains unclear, and further study is required to better understand the formation of choroidal polypoidal dilations in these conAccepted for publication Jun 21, 2006. From the Rabelais Ophthalmologic Center, Lyon, France (M.M.-F., M.Q.-E.M.); Department of Ophthalmology, Lyon E. Herriot University Hospital, Lyon, France (P.-L.C.); Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium (A.L.). Inquiries to Martine Mauget-Fay¨sse, MD, Rabelais Ophthalmologic Center, 12–14 rue Rabelais, 69003 Lyon, France; e-mail: centrerabelais@ wanadoo.fr
970
©
2006 BY
ditions. (Am J Ophthalmol 2006;142:970 –975. © 2006 by Elsevier Inc. All rights reserved.)
T
ILTED DISK SYNDROME IS ONE OF THE OCULAR MAL-
formations that is associated with malclosure of the embryonic optic fissure.1 Tilted optic disks are relatively common and occur in 1.6% of the optic nerves. This anomaly results from optic disk dysversion and/or torsion (pseudorotation of the superior pole of the optic disk, angulation of the optic cup axis inferonasally, and elevation of the superotemporal neuroretinal rim). The disk anomaly is only one component of tilted disk syndrome and is accompanied classically by the following signs: astigmatism (93%), myopia (66%), situs inversus of the retinal vessels (70%), peripapillary atrophy (65%), inferonasal chorioretinal thinning (5%), posterior staphyloma (18%), and visual field defects (19%).2 Posterior staphyloma is a feature common to both high myopia and tilted disk syndrome. Occasionally, patients with tilted disk syndrome or high myopia have visual loss that results from choroidal neovascularization or neurosensory macular detachment that mimics central serous chorioretinopathy.3–5 Interestingly, especially in patients with tilted disk syndrome, these lesions usually are located at the junction between the altered and normal chorioretina (at the edge of the staphyloma), which suggests a relationship between localized retinal pigment epithelium dysfunction and choroidal perfusion anomalies.3 Polypoidal choroidal vasculopathy is characterized by the presence of dilated, choroidal vascular channels of a branching abnormal vascular network that ended in orange, bulging, polyp-like dilations that elevate the retinal pigment epithelium. Polypoidal dilations are globular, well-defined, hyperfluorescent, round lesions that usually are seen better at the edge of an interconnecting vascular network in the venous phase of indocyanine green angiography (ICG-A).6 These lesions usually occur in the peripapillary, macular, and peripheral retinal regions. Associated features are recurrent hemorrhagic detachments of the retinal pigment
ELSEVIER INC. ALL
RIGHTS RESERVED.
0002-9394/06/$32.00 doi:10.1016/j.ajo.2006.06.063
12 20/50 Yes OS
Female 63 HMWS 6
PCV
IN
TDS ⫽ tilted disk syndrome; HMWS ⫽ high myopia with staphyloma; OD ⫽ right; OS ⫽ left.
20/25
20/200 Count fingers 20/80 20/25 20/60 Count fingers 20/30 20/25 No Yes Yes Yes 64 66 TDS TDS 4 5
Male Female
OD OD OS OD
–0.5 (–2 * 80°) –10 Before pseudophakia –10 Before pseudophakia –8.5 (–3 * 10°) Before pseudophakia –10.75 (–3.75 * 180°) Before pseudophakia
20/40 20/50 No 63 TDS 3
Female
OD
–9.25 (–1.5 * 0°)
20/60 20/80 No 74 TDS 2
Female
OS
–4 (–0.5 * 85°)
Laser (n ⫽ 3)
(n ⫽ 1)
63 72 30 12
17 with
5 with
5 No 74 TDS 1
Male
OD
–3.5 (–3 * 0°)
20/100
20/50
Photodynamic therapy verteporfin (n ⫽ 2) Photodynamic therapy verteporfin (n ⫽ 2) Photodynamic therapy verteporfin (n ⫽ 5) Laser (n ⫽ 3) None Photodynamic therapy Laser (n ⫽ 3)
with
Follow-Up (mo) Treatment Final Visual Acuity Initial Visual Acuity Refractive Error Pseudophakia Eye Gender Age (y) TDS and HMWS Patient
TABLE. Clinical Characteristics of Patients With Polypoidal Choroidal Vasculopathy in Tilted Disk Syndrome (Case 1 to 5) and High Myopia With Staphyloma (Case 6)
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FIGURE 1. Case 1, Top left: Fluorescein angiography shows area of leakage (black arrow) that was associated with a more hyperfluorescent spot at the site of the polypoidal dilation (white arrow). Top right: Indocyanine green angiogram (ICG-A) with polypoidal choroidal dilation (white arrow), atypical choroidal drainage venous routes and venous congestion with irregular and tortuous or possibly occluded choroidal veins. Bottom: Optical coherence tomography (OCT) scans (gray scale) shows circumscribed elevations with signs of rupture of the retinal pigment epithelium/choriocapillaris complex (white arrow) and a thin serous retinal detachment (open arrow).
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FIGURE 2. Case 2, Left: Fluorescein angiography shows area of leakage (black arrow) that was associated with a more hyperfluorescent spot at the site of the polypoidal dilation (white arrow). Right: Indocyanine green angiogram (ICG-A) with polypoidal choroidal dilation (white arrow), atypical choroidal drainage venous routes and venous congestion with irregular and tortuous or possibly occluded choroidal veins. Note the similarities between cases 1 and 2.
epithelium and serohemorrhagic retinal detachments with relatively minimal fibrous scarring. We discuss the characteristics of polypoidal choroidal vasculopathy in a consecutive case series of six patients (eight eyes) with tilted disk syndrome (TDS) or high myopia with staphyloma (HMWS). To the best of our AND
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FIGURE 3. Case 3, Left: Fluorescein angiography shows a large area of leakage associated with sub retinal hemorrhages and a temporal pigment epithelial detachment (white arrow). Right: Indocyanine green angiogram (ICG-A) shows polypoidal choroidal dilations (white circle).
FIGURE 4. Case 4, Left: Fluorescein angiography shows a large area of leakage. Right: Indocyanine green angiogram (ICG-A) shows polypoidal choroidal dilations (white circle) on the way of the superotemporal venous drainage.
knowledge, this is the first report of polypoidal choroidal vasculopathy complicating eyes with TDS or HMWS.
were Caucasian. TDS with polypoidal choroidal vasculopathy was present in five patients (six eyes); HMWS and polypoidal choroidal vasculopathy was present in one patient (two eyes). The mean refractive error of the affected eyes with TDS was ⫺6.8 ⫾ 3.7 diopters (range, ⫺1.5 to ⫺10 diopters). The TDS or HMWS was bilateral in all the study patients. One patient with TDS and the only patient with HMWS had bilateral polypoidal choroidal vasculopathy; this condition was unilateral in all the other patients. All the study patients had macular abnormalities and visual loss. The visual acuity at evaluation varied from “counting fingers” to 20/25. Fundus biomicroscopy (Figure 5) showed subretinal hemorrhages in all eyes. Five eyes also had lipoid exudates (cases 2, 3, 4, 5 OD and 6 OS). All the study eyes had a serous retinal detachment, with three eyes having combined serous pigment epithelial detachment (PED; Figures 3, 5, and 8). Polypoidal choroidal vasculopathy was discovered by fluorescein angiography in the left eye of case 6 (Figure 8). Fluorescein angiography highlighted the presence of hyperfluorescent zones, with pinpoints that correspond to areas of leakage and more hyperfluorescent spots at the site of the polypoidal dilations in all the study patients (Figures 1 to 8). ICG-A, which allowed the analysis of the choroidal vasculature, showed choroidal venous abnormalities with dilated and irregular drainage veins in the proximity of choroidal polypoidal dilations (Figures 1 to 8). These typically hyperfluorescent polypoidal abnormalities were better seen in the venous phase of ICG-A. All the polypoidal dilations were located at the junction between the staphyloma and the normal retina. The direction of the drainage of the veins with polypoidal dilations at inclusion was toward the superotemporal vortex vein. A feeder vessel was not demonstrated clearly in any study patient. The abnormal vascular network was well-defined as a plaque in the late phase. In one patient, a new drainage route appeared with a vaginal vein (Figure 5). On OCT scans (Figure 1), polypoidal dilations were identified as circumscribed elevations of the retinal pigment epithe-
METHODS THIS STUDY IS A RETROSPECTIVE, MULTICENTER, INTER-
ventional case series that was performed in compliance with the Declaration of Helsinki. All the study patients (six patients, eight eyes) were evaluated in the authors’ affiliated institutions between 1999 and 2006 with a diagnosis of TDS or HMWS and complicated with polypoidal choroidal vasculopathy. At each visit, a complete examination of both eyes was performed that included best-corrected visual acuity examination with the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, slit-lamp biomicroscopy, fluorescein angiography with the Topcon 50IA (Topcon, Inc, Paramus, New Jersey, USA), Topcon 50IX (Topcon, Inc, Paramus, New Jersey, USA), or OIS fundus cameras (Ophthalmic Imaging System, Sacramento, California, USA) and ICG-A with the Topcon 50IA or HRA 2 Heidelberg fundus camera (Heidelberg Engineering, GmbH, Dossenheim, Germany). Optical coherence tomography (OCT) scans (Zeiss Humphrey, Oberkochen, Germany) were performed after ICG-A over the area with choroidal polypoidal dilations and across the fovea (6 mm vertical and 6 mm perpendicular). The patients were treated, if required, with laser photocoagulation or verteporfin-photodynamic therapy (V-PDT). The main outcome measures were final visual acuity and angiographic and OCT scan features.
RESULTS THE RESULTS ARE SUMMARIZED IN THE TABLE; THE ANGIO-
graphic and OCT features of the study patients are shown in Figures 1 to 8. The mean age of the patients was 67.3 ⫾ 5.3 (SD) years (range, 63 to 74 years). There were two male patients and four female patients. All the patients 972
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FIGURE 5. Case 5, right eye. Top left: Fundus photograph at baseline shows a large subretinal hemorrhage, small lipoid exudates, and the presence of a temporal pigment epithelial detachment. Top right: Fluorescein angiography shows a hyperfluorescent leaking area in the maculopapillary region and confirms the pigment epithelial detachment seen on fundus photography (white arrow). Bottom: Spontaneous evolution of the choroidal venous blood flow is documented on indocyanine green angiogram (ICG-A) images. Initially, (Bottom left) a large pigment epithelial detachment is seen with a vascular network and numerous polypoidal dilations in the notch; afferent and efferent choroidal vessels are seen in the maculopapillary region. One year later (Middle bottom), the polypoidal dilations are larger and stain heavily. Another year later (Bottom right), the pigment epithelial detachment and polypoidal dilations have disappeared; venovenous anastomoses (circle) have developed that connect the inferotemporal area to a vaginal vein (white arrows) with progressive dilation of the new drainage route. This newly formed drainage route appears to have developed to reduce the previous venous congestion.
FIGURE 6. Case 5, left eye. Left: Fluorescein angiography shows a large area of leakage with pinpoints. Right: Indocyanine green angiogram (ICG-A) shows numerous small polypoidal choroidal dilations (white circle).
lium/choriocapillaris complex with, in the active phase, an optically mildly reflective heterogeneous filling that was associated with serous retinal detachment. At inclusion, OCT scans confirmed that three eyes had PEDs, although all eyes had serous retinal detachments and retinal thickening (Figure 1). Treatment was given to seven eyes, with laser photocoagulation in three eyes and V-PDT in four eyes. One eye with very poor vision at evaluation did not receive treatment (case 5 OD). After V-PDT, venous drainage improved with reduction in venous swelling and normalization of venous calibers; the choroid appeared to have remodeled. Visual acuity at the final visit had increased slightly in three eyes, decreased VOL. 142, NO. 6
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FIGURE 7. Polypoidal choroidal vasculopathy in high myopia with staphyloma in case 6, right eye. Left: Fluorescein angiography shows a small area of leakage with pinpoints next to linear changes of the retinal pigment epithelium temporal to the macula. Right: Indocyanine green angiogram (ICG-A) shows a small cluster of numerous polypoidal choroidal dilations.
slightly in three eyes, and was unchanged at 20/25 in one eye. In the only untreated eye, visual acuity remained at counting fingers. Of the four eyes with a posttreatment follow-up period of more than one year, only one eye had improved visual acuity.
DISCUSSION VISUAL LOSS BECAUSE OF MACULOPATHY IS NOT UNCOM-
mon in eyes with TDS or HMWS. We report, for the first AND
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FIGURE 8. Polypoidal choroidal vasculopathy in high myopia with staphyloma in case 6, left eye. Left: Fluorescein angiography shows numerous small polypoidal dilations (black arrows) that are associated with a pigment epithelial detachment (white arrow) in the early phase. Middle: In the later phases, progressive pooling of dye is noted in the polypoidal dilations (black arrow) and under the pigment epithelial detachment (white arrow). Moreover, intense focal subretinal leakage (open arrow) that is similar to central serous chorioretinopathy is noted at the nasal border of the pigment epithelial detachment; pinpoints are seen in a larger area. Right: Indocyanine green angiogram (ICG-A) shows numerous large polypoidal dilations that mostly are located close to the pigment epithelial detachment (black arrow) and an interconnecting network of vessels that correspond to the pinpoint lesions that are seen on the fluorescein angiography (white circle).
time, polypoidal choroidal vasculopathy as a complication of TDS or HMWS as another cause of visual loss in these patients. TDS usually is associated with low myopia.1 In this syndrome, macular pigmentary changes are observed in 11% of the patients, and macular complications are more frequent and severe in eyes with a higher degree of refractive error.7 In our report, patients with tilted disk had a mean refractive error of ⫺6.8 diopters. Pigmentary change of the retinal pigment epithelium at the crest of the staphyloma with areas of choroidal atrophy is a characteristic feature of both HMWS and TDS. Choroidal neovascularization usually arises in eyes with retinal pigment epithelium changes, in breaks in Bruch’s membrane, or in atrophic lesions.3,8 Vision loss in the fourth decade of life or later in TDS or in HMWS may be due to serous macular detachment and subretinal leakage that mimics central serous chorioretinopathy.9 The area of leakage is a site of retinal pigment epithelium dysfunction,4 which corresponds to the temporal margin of the inferonasal staphyloma in TDS and to the border of the staphyloma in patients with HMWS. Interestingly, polypoidal choroidal vasculopathy can also occur along with diffuse disturbances of the retinal pigment epithelium, which evokes the diagnosis of atypical central serous retinopathy or diffuse retinal epitheliopathy.10 In view of these observations, it is not surprising that, in TDS or HMWS, localized retinal pigment epithelium disturbances can have polypoidal choroidal vasculopathy. We suggest that polypoidal choroidal vasculopathy can result from different triggers: a vasogenic origin as in central serous chorioretinopathy, a dysplastic origin in TDS,9 and a degenerative origin in high myopia. ICG-A has provided evidence of abnormal choriocapillary blood flow in central serous chorioretinopathy. We did not observe, in our patients, any diffuse signs of hyperpermeability that are similar to those found in chronic central serous chorioretinopathy. However, choroidal dilations that are associated with PEDs, a characteristic feature of 974
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central serous chorioretinopathy, were detected in three of our patients with TDS/HMWS. Our patients of TDS/ HMWS that was complicated by polypoidal choroidal vasculopathy were different from classic idiopathic polypoidal choroidal vasculopathy. The abnormal vascular network was much less visible in the early phase of ICG-A and was more defined in the late phase of ICG-A as a plaque in all eyes. We observed angiographic similarities in our study patients (Figures 1 to 8). First, polypoidal choroidal vasculopathy always was located at the border between the hypoplastic and normal choroid at the temporal crest of the inferonasal posterior staphyloma. The hypovascularized choriocapillaries in this area of the staphyloma may have induced hypoxia that was followed by choroidal neovascularization. The difference of curvature in the area of the staphyloma may also cause blood flow disturbances that are similar to that seen in arteriovenous crossings that give rise to hypoxia and neovascularization and/or inducement of venous shunts and vascular dilations. Second, the choroidal veins in the area of polypoidal formations were dilated and irregular in all our patients, sometimes appearing similar to a process of choroidal phlebitis with slowed blood flow because of the anatomic impairment. The dilation of the choroidal veins could also be a compensatory vasodilation reflex to slow down the blood stream and protect the retina against ischemia.11 Giuffre7 reported that in patients with tilted disk syndrome, choroidal neovascularization developed in the inferotemporal edge of the staphyloma in areas with marked alterations of the retinal pigment epithelium and the frequent presence of vaginal veins (veins that drain in veins of the sheaths of the optic nerve rather than in the vortex veins). However, these vaginal veins probably were observed more easily because of the depigmentation of the retinal pigment epithelium. In one of our patients (Figure 5), a vaginal vein developed as if the previous superior drainage to the vortex vein was not effective any more. The development of new OF
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choroidal venous drainage routes that connect the sector of an occluded vortex vein to that of the intact vortex vein area with venovenous anastomoses is well-known.12,13 The choroidal venous flow alterations that are suspected on angiography must be confirmed by hemodynamic measurements. In a recent publication concerning tilted disk syndrome, ocular hemodynamic measurements that were determined by color Doppler ultrasonography were not altered in the ophthalmic artery, central retinal artery, central retinal vein, and posterior ciliary arteries. However, it is not possible to detect localized venous choroidal disturbances with color Doppler ultrasonography.14 More sophisticated techniques such as laser Doppler flowmetry might need to be used to characterize adequately the alterations in choroidal venous flow that are suspected on angiography. Our observations show that polypoidal choroidopathy is a sight threatening complication in eyes with TDS or high myopia with posterior staphyloma. Treatment can be considered in these patients either with laser coagulation or V-PDT. Although we obtained short-term favorable results after treatment and did not note adverse events, the longterm results are unknown, and there is a potential risk of late visual loss because of progressive atrophy of the scars in these myopic eyes.3 The eyes that were treated with V-PDT demonstrated significant improvement in venous drainage and calibers. The choroid appeared to have remodeled in these patients, which was consistent with the observations of Chan and associates15 after V-PDT in central serous chorioretinopathy. Chan and associates described the potential of V-PDT to narrow dilated choroidal vessels and to decrease choroidal permeability after V-PDT. In summary, we observed an abnormal vascular network with polypoidal formation in all our patients in the area between the hypoplastic and normal choroids: at the temporal crest of the inferonasal staphyloma in TDS or at the border of the posterior staphyloma in HMWS. Abnormal dilated and irregular choroidal veins, which are identical to what is frequently seen in diffuse retinal epitheliopathy or central serous chorioretinopathy, consistently were present close to the polypoidal dilations. However, the pathogenesis remains unclear, and further study is required to better understand the formation of choroidal polypoidal dilations in these conditions.
1. Apple DJ, Rabb MF, Walsh PM. Congenital anomalies of the optic disc. Surv Ophthalmol 1982;27:3– 41. 2. Vongphanit J, Mitchell P, Wang JJ. Population prevalence of tilted optic disc and the relationship of this sign to refractive error. Am J Ophthalmol 2002;133:679 – 685. 3. Leys AM, Cohen SY. Subretinal leakage in myopic eyes with a posterior staphyloma or tilted disk syndrome. Retina 2002;22: 659 – 665. 4. Theodossiadis PG, Grigoropoulos V, Emfietzoglou J, Theodossiadis GP. Optical coherence tomography study of tilted optic disk associated with macular detachment. Graefes Arch Clin Exp Ophthalmol 2006;244:122–124. 5. Stur M. Congenital tilted disk syndrome associated with parafoveal subretinal neovascularization. Am J Ophthalmol 1988;105:98 –99. 6. Ciardella AP, Donsoff IM, Huang SJ, et al. Polypoidal choroidal vasculopathy. Surv Ophthalmol 2004;49:25–37. 7. Giuffre G. Chorioretinal degenerative changes in the tilted disc syndrome. Int Ophthalmol 1991;15:1–7. 8. Quaranta M, Brindeau C, Coscas G, Soubrane G. Multiple choroidal neovascularizations at the border of a myopic posterior macular staphyloma. Graefes Arch Clin Exp Ophthalmol 2000;238:101–103. 9. Cohen SY, Quentel G, Guiberteau B, et al. Macular serous retinal detachment caused by subretinal leakage in tilted disc syndrome. Ophthalmology 1998;105:1831–1834. 10. Yannuzzi LA, Freund KB, Goldbaum M, et al. Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy. Ophthalmology 2000;107:767–777. 11. Hayreh SS, Chopdar A. Occlusion of the posterior ciliary artery: V, protective influence of simultaneous vortex vein occlusion. Arch Ophthalmol 1982;100:1481–1491. 12. Takahashi K, Kishi S. Remodeling of choroidal venous drainage after vortex vein occlusion following scleral buckling for retinal detachment. Am J Ophthalmol 2000;129: 191–198. 13. Hayreh SS, Baines JA. Occlusion of the vortex veins: an experimental study. Br J Ophthalmol 1973;57:217–238. 14. Tatlipinar S, Yagci B, Yaylali V, et al. The effect of tilted disc syndrome on ocular hemodynamic measurements. NeuroOphthalmology 2005;29:49 –52. 15. Chan WM, Lam DS, Lai TY, et al. Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level. Br J Ophthalmol 2003;87:1453–1458.
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Biosketch Martine Mauget-Faÿsse, MD, received her medical degree from Lyon University (France) and completed a post-doctoral training for retinal diseases at the Creteil Hospital. She was a consultant for retinal diseases at Bellevue Hospital in Saint-Etienne and Herriot Hospital in Lyon, France. Dr Mauget-Faÿsse has had an exclusive private practice since 2002. Her clinical expertise is in the diagnosis and management of retinal diseases, particularly in age-related macular degeneration and central serous chorioretinopathy. Dr Mauget-Faÿsse teaches low-vision and retinal diseases in Lyon University.
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Biosketch Pierre-Loïc Cornut, MD, is a graduate of Lyon University (France) and actually completed his internship at the Herriot Hospital. His area of research interest is the physiology of photoreception and the characterization of retinal mechanisms underlying the non-image-forming responses involving ganglion cells containing Melanopsin (Neurosciences Master, 2006). Dr Cornut is certified by the European Board of Ophthalmology, and is a member of the French Society of Ophthalmology and the Association for Research in Vision and Ophthalmology.
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