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Pulsatile Blood Flow in the Polypoidal Choroidal Vasculopathy
Pulsatile Blood Flow in the Polypoidal Choroidal Vasculopathy Akiko Okubo, MD,1 Motoko Ito, MD,1 Munefumi Sameshima, PhD,1 Akinori Uemura, MD,2 Taiji Sakamoto, MD1 Objective: To describe patients with pulsatile polypoidal vessels in polypoidal choroidal vasculopathy (PCV). Design: Retrospective, observational case series. Participants: Eighty-four eyes of 74 patients with PCV. Methods: The medical records of patients diagnosed with PCV between 1998 and 2004 at Kagoshima University Hospital were reviewed. Main Outcome Measures: A pulsatile polypoidal vessel (PV) on indocyanine green angiography (ICGA). Results: Seven of 74 patients (9.5%) had PVs in the macula. Four eyes revealed pulsatile PVs on the day the diagnosis of PCV was first made, and PVs in the other 3 eyes showed pulsatile movement during the follow-up period. Two patterns of pulsatile movement were observed on ICGA: (1) a rhythmic variation in the caliber of a choroidal vessel (caliber variation pattern) and (2) a pulsatile blood flow in a tortuous and relatively narrow choroidal vessel (pulsatile blood flow pattern). Both patterns of pulsatile PVs appeared in the early frames of the ICGA, and some of them were observable even during the first 15 minutes after the ICG dye injection. The pulsatile movement disappeared spontaneously without treatment in some patients, and the period in which pulsatile PVs was detectable on ICGA was limited in each patient. Conclusions: We report the features of pulsatile PV in PCV. It is a unique and important characteristic that has not been reported with any other chorioretinal diseases and may provide a clue to understanding the pathogenesis of PCV. Ophthalmology 2005;112:1436 –1441 © 2005 by the American Academy of Ophthalmology.
Polypoidal choroidal vasculopathy (PCV) has typical morphologic features: dilated, aneurysmal, spheroidal, polyplike structures at the termination of a branching network of large choroidal vessels seen as reddish-orange structures ophthalmoscopically, associated with recurrent serosanguineous detachments of the retinal pigment epithelium and neurosensory retina and retinal exudation.1–13 Clinically, the vascular abnormality appears to be in the inner choroid and is composed of 2 basic elements: a polypoidal vessel (PV) that projects internally from the inner choroid toward the outer retina and a branching vascular network. The pathogenesis of PCV remains unclear. Some clinicopathologic studies suggest that the polypoidal vessel represents choroidal neovascularization,14 –16 whereas others
Originally received: January 8, 2005. Accepted: March 10, 2005. Manuscript no. 2005-21. 1 Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 2 Kagoshima City Hospital, Kagoshima, Japan. Supported by the Japanese Ministry of Education, Science, Sports and Culture, Tokyo, Japan (research grant no.: 17591844). The authors have no propriety interests. Correspondence to Akiko Okubo, Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. E-mail: akiko@m2. kufm.kagoshima-u.ac.jp.
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© 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
suggest that it represents an abnormality of the inner choroidal vasculature.17–19 Thin-walled dilated vessels varying in size, which are regarded as being of venular origin, are commonly found in PCV and are thought to account for PVs.14 –19 Some studies suggest arterioles contribute to the polypoidal lesion.16 –19 Polypoidal vessels are commonly found in the peripapillary and macular regions. Only rare reports of pulsatile movement in the choroidal vasculature during indocyanine green angiography (ICGA) have been published in the ophthalmic literature,20 –22 and the practical implication of this phenomenon is uncertain. This interesting finding of pulsatile movements in PVs may provide a clue to understanding the pathogenesis of PCV. In this current study, we review our series of cases of PCV with pulsatile PVs and discuss possible mechanisms for this curious phenomenon.
Patients and Methods A retrospective review identified 84 eyes of 74 patients diagnosed with PCV during the period between July, 1998, and April, 2004, at Kagoshima University Hospital. All patients underwent comprehensive ophthalmologic examination, including best-corrected visual acuity, intraocular pressure, biomicroscopy, dilated funduscopic examination, fluorescein angiography, and ICGA (Topcon, Tokyo, Japan). The clinical diagnosis of PCV was based on the presence of PVs on ICGA corresponding to clinically visible ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2005.03.017
Okubo et al 䡠 Pulsatile Polypoidal Vessels in PCV reddish-orange lesions on fundus examination. We reviewed every ICGA on videotape, and the procedure was repeated periodically for each eye during the follow-up period. The characteristics of pulsatile PVs were determined by at least 2 independent observers (AO, MI).
Results A total of 84 eyes of 74 Japanese patients met the study criteria. Patients ranged in age from 47 to 91 years (mean⫾standard deviation, 68.0⫾8.7 years). Sixty-four (86.5%) had unilateral eye involvement and 10 had bilateral involvement. Men were predominantly affected (71.6%). Mean follow-up time after diagnosis of PCV was 23.3 months (range, 1–71 months). Thirty-three patients (44.6%) were being treated for systemic hypertension, hypercholesterolemia, or both.
Patients with Pulsatile Polypoidal Vessels Seven of 74 patients (9.5%) had pulsatile PVs. Demographics are presented in Table 1. Patients ranged in age from 50 to 87 years (mean⫾SD, 65.3⫾13.1 years). Two patients were female and 5 were male. Four eyes revealed pulsatile PV on the day the diagnosis of PCV was first made, and the PVs in the other 3 eyes showed pulsatile movement during the follow-up period. All of the pulsatile PVs were located in the macula. In 1 eye, the pulsatile PVs were detected at 2 separate sites, whereas the other eyes demonstrated pulsatile movement at a single site. In 3 eyes, pulsatile PVs disappeared spontaneously without treatment—after laser photocoagulation in 1 eye and after sub-Tenon injection of triamcinolone acetonide in another eye. Two patterns of pulsatile movement corresponding to the patients’ radial pulse were observed on the ICGA: (1) a rhythmic variation in the caliber of a choroidal vessel (caliber variation pattern) and (2) a pulsatile blood flow in a tortuous and relatively narrow choroidal vessel (pulsatile blood flow pattern). Both patterns of pulsatile PVs appeared in the early frames of the ICGA and showed leakage of dye. The pulsatile movement was detectable 15 minutes after the injection of ICG dye in some patients. In other patients, the pulsatile movement was less visible after the first few minutes because of marked leakage of dye from the pulsatile PVs. The pulsatile movements were not visible ophthalmoscopically.
Case Reports Patient 1. An 87-year-old man had blurred vision in his right eye for 2 months. His left ocular fundus showed atrophic scarring with pigmentation in the macula. Visual acuity was 20/200 in the right eye and 20/600 in the left eye. Fundus examination of the right eye revealed several subretinal reddish-orange nodules in the macula with pigmentary changes (Fig 1A). The ICGA of the late choroidal arteriolar filling phase or early choroidal venular filling phase revealed a pulsatile choroidal vessel temporal to the fovea followed by the appearance of tortuous network of vessels with several beaded polypoidal dilations in the macula (Fig 1B, C). The pulsatile vessel showed rhythmic movement with apparent vasodilation and vasoconstriction (caliber variation pattern; Fig 1B, C, arrows; Video 1 [available at http://aaojournal.org]). The pulsatile movement was detectable for 21 minutes after dye injection. The pulsatile PV leaked dye to form a relatively large polypoidal structure corresponding to the reddish-orange nodule (Fig 1A, arrow). Repeat ICGA was not performed, because no significant changes (i.e., subretinal hemorrhage, vitreous hemorrhage, or both) occurred during 47 months of follow-up. The reddish-orange nodules in the macula became white.
Patient 5. A 55-year-old woman experienced distortion of vision in her right eye that lasted for 1 week. Visual acuity was 20/16 in each eye. Fundus examination of the right eye revealed a reddish-orange lesion associated with serous retinal detachment, hard exudates, and subretinal hemorrhage temporal to the fovea. On ICGA at the first examination, a pulsatile inflow (back and forth movements of dye) in a choroidal vein near the superotemporal vascular arcade was observed during the first few seconds after dye injection (Fig 2A, B, E). A beaded vessel (Fig 2B, arrowhead), with pulsation not yet visible at this time, also appeared temporal to the fovea. Ten weeks later, serous detachment and subretinal hemorrhage extended toward the fovea, and visual acuity deteriorated to 20/30 (Fig 2C). On ICGA, pulsatile movements appeared with rhythmic variations in the caliber of the PV (Fig 2D, E, yellow polypoidal structure) during the first few minutes (caliber variation pattern). Five weeks later, ICGA revealed disappearance of the PV pulsation, but not the pulsatile inflow in the choroidal vein near the superotemporal vascular arcade, and showed an increase of PVs. Laser photocoagulation was applied to the PVs, resulting in resolution of the reddishorange lesion, serous retinal detachment, and subretinal hemorrhage. The ICGAs performed at 1 and 4 months after laser photocoagulation revealed the disappearance of both PVs and pulsatile abnormal inflow in the choroidal vein. Patient 6. An asymptomatic 63-year-old man was referred for further evaluation after retinal pigment epithelium detachment in the right eye was found during routine examination. Visual acuity was 20/25 in the right eye. Ophthalmoscopy of the right eye revealed orange elevations of the retinal pigment epithelium (approximately 1.5 ⫻ 1.0 disc diameters) with 2 reddish-orange nodules (Fig 3A). In the late choroidal arteriolar filling phase or early choroidal venular filling phase of ICGA, 2 relatively narrow tortuous choroidal vessels with pulsatile flow appeared at the center of the fovea and inferonasal to the fovea (Fig 3B). The blood flow in a narrowed or constricted region of each tortuous choroidal vessel exhibited a higher, rhythmic velocity with slowing of blood flow distal to the narrowed or constricted region (pulsatile blood flow pattern; Video 2 [available at http:// aaojournal.org]). The advancing edge of dye in these tortuous choroidal vessels proceeded slowly (Fig 3C–F), with dye leaking in the venular filling phase corresponding to the reddish-orange nodules. Pulsatile movements were observed simultaneously in the 2 PVs: the pulsatile movement of the PV at the center of the fovea was distinct and detectable for 14 minutes after dye injection, whereas the pulsatile movement of the other PV was less distinct and continued during the first 5 minutes. The patient was diagnosed with PCV and underwent subsequent ICGA. The pulsatile movement of the PV inferonasal to the fovea was detectable on ICGAs after 3 months and disappeared after 6 months, corresponding to resolution of the reddish-orange nodule. The pulsatile movement of the PV at the center of the fovea persisted after 3 and 6 months. On ICGA after 12 months, a weak pulsatile movement was still detectable, but on the ICGA after 15 months, no pulsation was observed.
Discussion We examined 74 Japanese cases with PCV retrospectively and found pulsatile PVs in 7 patients (9.5%). No reports in the English literature are available on pulsatile PV, although there are a few brief descriptions in the Japanese literature.20 –22 Notably, the period of pulsatile PVs detectable on ICGA is limited in each case. In patient 5, the pulsatile movement of PV disappeared within 5 weeks. In patient 6,
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Ophthalmology Volume 112, Number 8, August 2005 Table 1. Clinical Characteristics of Patient No.
Age (yrs)
Gender
Affected Eye
No. of Pulsatile PV
Location of Pulsatile PV
Pattern of Pulsation
Duration of Pulsation (min)*
1 2 3 4 5 6 7
87 75 50 71 55 63 56
M M M F F M M
Right Right Right Right Right Right Left
1 1 1 1 1 2 1
Macula Macula Macula Macula Macula Macula Macula
C PBF C C C PBF C
21 2 2 3 2 14, 5 3
C ⫽ caliber variation pattern; F ⫽ female; M ⫽ male; PBF ⫽ pulsatile blood flow pattern; PV ⫽ pulsatile vessel. *Observable duration of the pulsation of PV on ICGA after dye injection. † Time interval between the appearance and the disappearance of pulsation on ICGA. ‡ After laser photocoagulation. § After sub-Tenon triamcinolone acetonide.
the pulsatile movement of 2 PVs was observed for at least 6 to 15 months and disappeared spontaneously. The pulsatile movement may disappear without treatment in some cases, with or without resolution of the reddish-orange nodules. Thus, pulsatile PVs are not always associated with massive subretinal hemorrhage, as suggested by some investigators.20,21 The pulsatile PVs appeared in the late choroidal arteriolar filling phase or early choroidal venular filling phase, and some were observable even during the first 15 minutes after ICG dye injection. The pulsatile movement of PVs may be classified into 2 patterns on ICGA in the present study: (1) a rhythmic movement of the vessel wall with apparent vasodilation and vasoconstriction (caliber variation pattern) and (2) a pulsatile blood flow in a tortuous, relatively narrow choroidal vessel (pulsatile blood flow pattern). In the latter pattern, the blood flow in a narrowed or constricted region of the tortuous choroidal vessel exhibited higher, rhythmic velocity and slowing of blood flow distal to the narrowed or constricted region. These 2 patterns may represent a single phenomenon viewed from different angles. We speculate that the vasoarchitecture is such that a venule is narrowed or constricted by a crossing arteriole and is dilated at the poststenotic portion, resulting in hyperperme-
ability. These features suggest focal venous stasis. In this setting, the choroidal venule might be susceptible to the pulse wave, with the stenotic region exhibiting greater blood flow (i.e., velocity) and the poststenotic region exhibiting caliber variation. To our knowledge, PCV is the only choroidal vascular disease in which such pulsatile movements in blood vessels have been observed on ICGA. Pulsation has not been well documented in either physiologic or pathologic choroidal vessels. Bischoff et al23 examined the choroidal circulation of 173 patients using scanning laser ICGA and found a choroidal pulsation in the macular region in 94 (54%): 84% of these patients exhibited this pulsation during the first few seconds after the inflow of ICG, and this was believed to be a physiological phenomenon. Sixteen of 94 cases revealed a localized pulsation of longer duration (10 –15 seconds) with back and forth movements of dye in 1 or a few choroidal veins. This pulsation with a longer duration was regarded as abnormal and possibly reflected phasic pressure changes in choroidal veins with low flow or direct transmission of the pulsation from an arteriole to a venule (arteriovenous shunt or arteriovenous crossing). The abnormal inflow (back and forth movements) in the choroidal vein of patient 5 (which occurred 10 weeks before the appearance of pulsatile move-
Figure 1. A, Color fundus photograph of patient 1 showing several reddish-orange nodules in the macula with pigmentary change, right eye. Arrow indicates the same site as the arrows in Fig 2B, C. B and C, Indocyanine green angiograms taken 60 and 63 seconds after dye injection indicating network vessels with several beaded polypoidal lesions in the macula. Note the change in the caliber of the polypoidal vessel (arrows) between the 2 frames. The pulsatile vessel shows a rhythmic movement such that its caliber appeared (B) dilated and (C) constricted (caliber variation pattern). See also video 1 (available at http://aaojournal.org).
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Okubo et al 䡠 Pulsatile Polypoidal Vessels in PCV Patients with Pulsatile Polypoidal Vessel Onset of Pulsation
Disappearance of Pulsation
Period of Pulsation (mos)†
Final Best-Corrected Visual Acuity
Follow-up period (mos)
General Condition
At first examination During follow-up At first examination During follow-up During follow-up At first examination At first examination
Unknown Yes Yes‡ No Yes Yes Yes§
Unknown 5 3 3 1 6, 15 2
20/1000 20/40 20/20 20/63 20/500 20/30 20/20
51 36 28 24 23 19 15
None None Arrhythmia Hypertension Hypercholesterolemia Hypertensive cardiac disease None
ments in a PV) seems to represent this type of pulsatile inflow. In contrast to the pulsatile choroidal inflow described by Bischoff et al, the pulsatile movement of PVs in the present study appeared in the late choroidal arteriolar filling phase or the early venular filling phase, and some were observable even in the late choroidal venous filling phase. This implies that the pulsatile movement of PV does not reflect a mere physiologic phenomenon. An unusual pulsation is known to occur in various tissues.24 –29 Some arterial aneurysms, including retinal macroaneurysms show a pulsatile movement.24 –26 Veins have also exhibited pulsatile movement under normal and some
unusual conditions: jugular venous pulse, pulsatile varicose veins,27,28 pulsatile femoral veins29 resulting from a retrograde pulsatile flow caused by elevated right-atrial pressure; arteriovenous shunt (AVS) and a vein neighboring an artery, in which the arteriolar pulse wave is directly transmitted to the vein. Considering the phase of its appearance and the long duration on ICGA, the pulsatile movement of PV observed in this study seems to relate to an AVS or neighboring arteriovenous crossing. In the retina, Tanaka et al30 reported that AVS at the arteriovenous crossing could occur in retinal vascular diseases such as branch retinal vein occlusion and
Figure 2. A and B, Sequential indocyanine green angiograms (ICGAs) of patient 5 taken (A) 16 and (B) 18 seconds after dye injection (at presentation) indicating a beaded vessel (arrowhead) temporal to the fovea and an abnormal pulsatile inflow (back and forth movements) in a choroidal vein (arrows) inferior to the superotemporal vascular arcade. Note the change in the width of the dye flow (arrows) in the choroidal vein between the 2 frames. C, Fundus photograph 10 weeks later showing a reddish-orange lesion (arrowhead) associated with hard exudates, subretinal hemorrhage, and serous retinal detachment in the macula. D, Early choroidal venular filling phase from ICGA taken on the same day as in C showing a pulsatile polypoidal vessel. E, Schematic representation of the choroidal vessels within the outlined portion in Fig 2D. Yellow polypoidal structure indicates a pulsatile vessel with rhythmic variations in the caliber. Red arrows indicate abnormal pulsatile inflow (back and forth movements) in the choroidal vein.
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Figure 3. A, Color fundus photograph of patient 6 reveals 2 reddish-orange nodules at the center of the fovea (black arrowhead) and inferonasal to the fovea (white arrowhead), accompanied by shallow neurosensory detachment in the macular region, right eye. B–E, Sequential indocyanine green angiograms of the same subject taken (B) 32 seconds, (C) 36 seconds, (D) 51 seconds, and (E) 61 seconds after dye injection showing 2 polypoidal vessels (arrows) corresponding to the reddish-orange nodules. Note the time taken after dye injection of each frame and the speed of the dye filling after passing a narrow portion of the tortuous choroidal vessel at the center of the fovea. F, Schematic representation of the blood flow in the polypoidal vessel at the center of the fovea. The blood flow within a narrow portion (curved red arrow) of the tortuous vessel shows higher velocity, while the dye filling within the post-stenotic portion (curved green arrow) proceeds slowly (pulsatile blood flow pattern). See also video 2 (available at http://aaojournal.org).
retinal artery occlusion. The same authors stated that the vessels, particularly veins at an arteriovenous crossing where the artery and the vein have a common adventitia, show vasodilation and hyperpermeability in response to a decrease in perfusion pressure, and direct inflow from artery to vein occurs when vasodilation and hyperpermeability are prolonged. The filling delay of the dye, which was found most prominently in the pulsatile flow pattern in the present study, seems to indicate stasis peripheral to the PV. The abnormal inflow (back and forth movement) of the choroidal vessel near the PV that became pulsatile 10 weeks later in patient 5 seems to reflect phasic pressure changes in low-flow choroidal veins, as suggested by Bischoff et al.23 These findings imply that focal venous stasis could exist followed by vasodilation and hyperpermeability in the choroid. We could not confirm the positional relationship between pulsatile PVs and arteriovenous crossings in the present study, because numerous choroidal vessels at different levels appear simultaneously on ICGA. However, previous clinicopathologic studies16 –18 have shown a close relationship between pathologic choroidal venules and arterioles in PCV: a tortuous, aneurysmally dilated choroidal venule manifesting hyperpermeability and an arteriole showing sclerosis had common adventitia, apparently forming an arteriovenous crossing. In these situations, AVS also may develop as seen in the retina.30 In the choroid, arterioles and venules frequently intersect, particularly within the macular and peripapillary areas, and the choroidal ves-
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sels in these areas are tortuous.31–35 In addition, vascular tortuousness increases with arteriosclerosis. All of these features may be associated with AVS. Herein, we report the features of pulsatile PVs in PCV. Although we could not identify the exact mechanism of this phenomenon, it is possible that pulsatile PVs reflect sites of AVS or arteriovenous crossing in the choroidal vasculature as suggested by our ICGA findings. Further elucidation of this phenomenon of pulsatile movement in PVs might be helpful in understanding the pathogenesis of PCV. Acknowledgments. The authors thank Dr Teruto Hashiguchi of the Department of Laboratory and Vascular Medicine and Dr Masaaki Miyata of the Department of Cardiovascular, Respiratory and Metabolic Medicine in Kagoshima University Graduate School of Medical and Dental Sciences for helpful discussion to interpret the pulsatile blood flow.
References 1. 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. 2. Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic choroidal vasculopathy (IPCV). Retina 1990;10:1– 8. 3. Kleiner RC, Brucker AJ, Johnston RL. The posterior uveal bleeding syndrome. Retina 1990;10:9 –17. 4. Perkovich BT, Zakov ZN, Berlin LA, et al. An update on
Okubo et al 䡠 Pulsatile Polypoidal Vessels in PCV
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multiple recurrent serosanguineous retinal pigment epithelial detachments in black women. Retina 1990;10:18 –26. Spaide RF, Yannuzzi LA, Slakter JS, et al. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina 1995;15:100 –10. 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. Uyama M, Matsubara T, Fukushima I, et al. Idiopathic polypoidal choroidal vasculopathy in Japanese patients. Arch Ophthalmol 1999;117:1035– 42. Yannuzzi LA, Wong DWK, Sforzolini BS, et al. Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration. Arch Ophthalmol 1999;117:1503–10. Iijima H, Iida T, Imai M, et al. Optical coherence tomography of orange-red subretinal lesions in eyes with idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol 2000;129: 21– 6. Ahuja RM, Stanga PE, Vingerling JR, et al. Polypoidal choroidal vasculopathy in exudative and haemorrhagic pigment epithelial detachments. Br J Ophthalmol 2000;84;479 – 84. Uyama M, Wada M, Nagai Y, et al. Polypoidal choroidal vasculopathy: natural history. Am J Ophthalmol 2002;133: 639 – 48. Sho K, Takahashi K, Yamada H, et al. Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics. Arch Ophthalmol 2003;121:1392– 6. Ciardella AP, Donsoff IM, Huang SJ, et al. Polypoidal choroidal vasculopathy. Surv Ophthalmol 2004;49:25–37. Lafaut BA, Aisenbrey S, van den Broecke C, et al. Polypoidal choroidal vasculopathy pattern in age-related macular degeneration: a clinicopathologic correlation. Retina 2000; 20:650 – 4. Terasaki H, Miyake Y, Suzuki T, et al. Polypoidal choroidal vasculopathy treated with macular translocation: clinical pathological correlation. Br J Ophthalmol 2002;86:321–7. Rosa RH Jr, Davis JL, Eifrig CW. Clinicopathologic correlation of idiopathic polypoidal choroidal vasculopathy. Arch Ophthalmol 2002;120:502– 8. Okubo A, Sameshima M, Uemura A, et al. Clinicopathological correlation of polypoidal choroidal vasculopathy revealed by ultrastructural study. Br J Ophthalmol 2002;86:1093– 8. Kuroiwa S, Tateiwa H, Hisatomi T, et al. Pathologic features of surgically excised polypoidal choroidal vasculopathy membranes. Clin Experiment Ophthalmol 2004;32:292–302. Nakajima M, Yuzawa M, Shimada H, Mori R. Correlation between indocyanine green angiographic findings and histo-
20. 21. 22. 23. 24. 25. 26. 27. 28. 29.
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pathology of polypoidal choroidal vasculopathy. Jpn J Ophthalmol 2004;48:249 –55. Furusho F, Imaizumi H, Takeda M. Polypoidal choroidal vasculopathy showing evident on indocyanine green angiography [in Japanese]. Atarashii Ganka 2000;17:1695–9. Fujiwara T, Hara Y, Sekiryu T. A case of idiopathic polypoidal choroidal vasculopathy (IPCV) with pulsatile polypoidal structure [in Japanese]. Ganka 2001;43:1365–70. Mori R, Yuzawa M, Kawamura A, et al. ICG angiographic findings of polypoidal choroidal vasculopathy by Heidelberg retina angiography (HRA) [in Japanese]. Ganka 2004;46:193–9. Bischoff P, Niederberger H, Weinacht S. Observations of the choroidal pulsation [in German]. Klin Monatsbl Augenheilkd 1996;208:318 –20. Burns DK, Kumar V. Blood vessels. In: Kumar V, Cotran RS, Robbins SL, eds. Basic Pathology. 6th ed. Philadelphia: WB Saunders; 1997:325–360. Shults WT, Swan KC. Pulsatile aneurysms of the retinal arterial tree. Am J Ophthalmol 1974;77:304 –9. Schneider U, Wagner AL, Kreissig I. Indocyanine green videoangiography of hemorrhagic retinal arterial macroaneurysms. Ophthalmologica 1997;211:115– 8. Moawad MR, Blair SD. Pulsating varicose veins. Lancet 1998;352:1030. Haimovici H. Arteriovenous shunting in varicose veins: its diagnosis by Doppler ultrasound flow detector. J Vasc Surg 1985;2:684 –91. Abu-Yousef MM, Kakish ME, Mufid M. Pulsatile venous Doppler flow in lower limbs: highly indicative of elevated right atrium pressure. AJR Am J Roentgenol 1996;167:977– 80. Tanaka T, Muraoka K, Tokui K. Retinal arteriovenous shunt at the arteriovenous crossing. Ophthalmology 1998;105: 1251– 8. Ashton N. Observations on the choroidal circulation. Br J Ophthalmol 1952;36;465– 81. Wybar KC. A study of the choroidal circulation of the eye in man. J Anat 1954;88:94 – 8. Ring HG, Fujino T. Observations on the anatomy and pathology of the choroidal vasculature. Arch Ophthalmol 1967;78: 431– 44. Yoneya S, Tso MO. Angioarchitecture of the human choroid. Arch Ophthalmol 1987;105:681–7. Fryczkowski AW. The choriocapillaris: anatomic and functional choroidal lobules. In: Yannuzzi LA, Flower RW, Slakter JS, eds. Indocyanine Green Angiography. St. Louis: Mosby; 1997:29 –35.
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Polypoidal choroidal vasculopathy (PCV) has typical morphologic features: dilated, aneurysmal, spheroidal, polyplike structures at the termination of a branching network of large choroidal vessels seen as reddish-orange structures ophthalmoscopically, associated with recurrent serosanguineous detachments of the retinal pigment epithelium and neurosensory retina and retinal exudation.1–13 Clinically, the vascular abnormality appears to be in the inner choroid and is composed of 2 basic elements: a polypoidal vessel (PV) that projects internally from the inner choroid toward the outer retina and a branching vascular network. The pathogenesis of PCV remains unclear. Some clinicopathologic studies suggest that the polypoidal vessel represents choroidal neovascularization,14 –16 whereas others
Originally received: January 8, 2005. Accepted: March 10, 2005. Manuscript no. 2005-21. 1 Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. 2 Kagoshima City Hospital, Kagoshima, Japan. Supported by the Japanese Ministry of Education, Science, Sports and Culture, Tokyo, Japan (research grant no.: 17591844). The authors have no propriety interests. Correspondence to Akiko Okubo, Department of Ophthalmology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan. E-mail: akiko@m2. kufm.kagoshima-u.ac.jp.
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© 2005 by the American Academy of Ophthalmology Published by Elsevier Inc.
suggest that it represents an abnormality of the inner choroidal vasculature.17–19 Thin-walled dilated vessels varying in size, which are regarded as being of venular origin, are commonly found in PCV and are thought to account for PVs.14 –19 Some studies suggest arterioles contribute to the polypoidal lesion.16 –19 Polypoidal vessels are commonly found in the peripapillary and macular regions. Only rare reports of pulsatile movement in the choroidal vasculature during indocyanine green angiography (ICGA) have been published in the ophthalmic literature,20 –22 and the practical implication of this phenomenon is uncertain. This interesting finding of pulsatile movements in PVs may provide a clue to understanding the pathogenesis of PCV. In this current study, we review our series of cases of PCV with pulsatile PVs and discuss possible mechanisms for this curious phenomenon.
Patients and Methods A retrospective review identified 84 eyes of 74 patients diagnosed with PCV during the period between July, 1998, and April, 2004, at Kagoshima University Hospital. All patients underwent comprehensive ophthalmologic examination, including best-corrected visual acuity, intraocular pressure, biomicroscopy, dilated funduscopic examination, fluorescein angiography, and ICGA (Topcon, Tokyo, Japan). The clinical diagnosis of PCV was based on the presence of PVs on ICGA corresponding to clinically visible ISSN 0161-6420/05/$–see front matter doi:10.1016/j.ophtha.2005.03.017
Okubo et al 䡠 Pulsatile Polypoidal Vessels in PCV reddish-orange lesions on fundus examination. We reviewed every ICGA on videotape, and the procedure was repeated periodically for each eye during the follow-up period. The characteristics of pulsatile PVs were determined by at least 2 independent observers (AO, MI).
Results A total of 84 eyes of 74 Japanese patients met the study criteria. Patients ranged in age from 47 to 91 years (mean⫾standard deviation, 68.0⫾8.7 years). Sixty-four (86.5%) had unilateral eye involvement and 10 had bilateral involvement. Men were predominantly affected (71.6%). Mean follow-up time after diagnosis of PCV was 23.3 months (range, 1–71 months). Thirty-three patients (44.6%) were being treated for systemic hypertension, hypercholesterolemia, or both.
Patients with Pulsatile Polypoidal Vessels Seven of 74 patients (9.5%) had pulsatile PVs. Demographics are presented in Table 1. Patients ranged in age from 50 to 87 years (mean⫾SD, 65.3⫾13.1 years). Two patients were female and 5 were male. Four eyes revealed pulsatile PV on the day the diagnosis of PCV was first made, and the PVs in the other 3 eyes showed pulsatile movement during the follow-up period. All of the pulsatile PVs were located in the macula. In 1 eye, the pulsatile PVs were detected at 2 separate sites, whereas the other eyes demonstrated pulsatile movement at a single site. In 3 eyes, pulsatile PVs disappeared spontaneously without treatment—after laser photocoagulation in 1 eye and after sub-Tenon injection of triamcinolone acetonide in another eye. Two patterns of pulsatile movement corresponding to the patients’ radial pulse were observed on the ICGA: (1) a rhythmic variation in the caliber of a choroidal vessel (caliber variation pattern) and (2) a pulsatile blood flow in a tortuous and relatively narrow choroidal vessel (pulsatile blood flow pattern). Both patterns of pulsatile PVs appeared in the early frames of the ICGA and showed leakage of dye. The pulsatile movement was detectable 15 minutes after the injection of ICG dye in some patients. In other patients, the pulsatile movement was less visible after the first few minutes because of marked leakage of dye from the pulsatile PVs. The pulsatile movements were not visible ophthalmoscopically.
Case Reports Patient 1. An 87-year-old man had blurred vision in his right eye for 2 months. His left ocular fundus showed atrophic scarring with pigmentation in the macula. Visual acuity was 20/200 in the right eye and 20/600 in the left eye. Fundus examination of the right eye revealed several subretinal reddish-orange nodules in the macula with pigmentary changes (Fig 1A). The ICGA of the late choroidal arteriolar filling phase or early choroidal venular filling phase revealed a pulsatile choroidal vessel temporal to the fovea followed by the appearance of tortuous network of vessels with several beaded polypoidal dilations in the macula (Fig 1B, C). The pulsatile vessel showed rhythmic movement with apparent vasodilation and vasoconstriction (caliber variation pattern; Fig 1B, C, arrows; Video 1 [available at http://aaojournal.org]). The pulsatile movement was detectable for 21 minutes after dye injection. The pulsatile PV leaked dye to form a relatively large polypoidal structure corresponding to the reddish-orange nodule (Fig 1A, arrow). Repeat ICGA was not performed, because no significant changes (i.e., subretinal hemorrhage, vitreous hemorrhage, or both) occurred during 47 months of follow-up. The reddish-orange nodules in the macula became white.
Patient 5. A 55-year-old woman experienced distortion of vision in her right eye that lasted for 1 week. Visual acuity was 20/16 in each eye. Fundus examination of the right eye revealed a reddish-orange lesion associated with serous retinal detachment, hard exudates, and subretinal hemorrhage temporal to the fovea. On ICGA at the first examination, a pulsatile inflow (back and forth movements of dye) in a choroidal vein near the superotemporal vascular arcade was observed during the first few seconds after dye injection (Fig 2A, B, E). A beaded vessel (Fig 2B, arrowhead), with pulsation not yet visible at this time, also appeared temporal to the fovea. Ten weeks later, serous detachment and subretinal hemorrhage extended toward the fovea, and visual acuity deteriorated to 20/30 (Fig 2C). On ICGA, pulsatile movements appeared with rhythmic variations in the caliber of the PV (Fig 2D, E, yellow polypoidal structure) during the first few minutes (caliber variation pattern). Five weeks later, ICGA revealed disappearance of the PV pulsation, but not the pulsatile inflow in the choroidal vein near the superotemporal vascular arcade, and showed an increase of PVs. Laser photocoagulation was applied to the PVs, resulting in resolution of the reddishorange lesion, serous retinal detachment, and subretinal hemorrhage. The ICGAs performed at 1 and 4 months after laser photocoagulation revealed the disappearance of both PVs and pulsatile abnormal inflow in the choroidal vein. Patient 6. An asymptomatic 63-year-old man was referred for further evaluation after retinal pigment epithelium detachment in the right eye was found during routine examination. Visual acuity was 20/25 in the right eye. Ophthalmoscopy of the right eye revealed orange elevations of the retinal pigment epithelium (approximately 1.5 ⫻ 1.0 disc diameters) with 2 reddish-orange nodules (Fig 3A). In the late choroidal arteriolar filling phase or early choroidal venular filling phase of ICGA, 2 relatively narrow tortuous choroidal vessels with pulsatile flow appeared at the center of the fovea and inferonasal to the fovea (Fig 3B). The blood flow in a narrowed or constricted region of each tortuous choroidal vessel exhibited a higher, rhythmic velocity with slowing of blood flow distal to the narrowed or constricted region (pulsatile blood flow pattern; Video 2 [available at http:// aaojournal.org]). The advancing edge of dye in these tortuous choroidal vessels proceeded slowly (Fig 3C–F), with dye leaking in the venular filling phase corresponding to the reddish-orange nodules. Pulsatile movements were observed simultaneously in the 2 PVs: the pulsatile movement of the PV at the center of the fovea was distinct and detectable for 14 minutes after dye injection, whereas the pulsatile movement of the other PV was less distinct and continued during the first 5 minutes. The patient was diagnosed with PCV and underwent subsequent ICGA. The pulsatile movement of the PV inferonasal to the fovea was detectable on ICGAs after 3 months and disappeared after 6 months, corresponding to resolution of the reddish-orange nodule. The pulsatile movement of the PV at the center of the fovea persisted after 3 and 6 months. On ICGA after 12 months, a weak pulsatile movement was still detectable, but on the ICGA after 15 months, no pulsation was observed.
Discussion We examined 74 Japanese cases with PCV retrospectively and found pulsatile PVs in 7 patients (9.5%). No reports in the English literature are available on pulsatile PV, although there are a few brief descriptions in the Japanese literature.20 –22 Notably, the period of pulsatile PVs detectable on ICGA is limited in each case. In patient 5, the pulsatile movement of PV disappeared within 5 weeks. In patient 6,
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Ophthalmology Volume 112, Number 8, August 2005 Table 1. Clinical Characteristics of Patient No.
Age (yrs)
Gender
Affected Eye
No. of Pulsatile PV
Location of Pulsatile PV
Pattern of Pulsation
Duration of Pulsation (min)*
1 2 3 4 5 6 7
87 75 50 71 55 63 56
M M M F F M M
Right Right Right Right Right Right Left
1 1 1 1 1 2 1
Macula Macula Macula Macula Macula Macula Macula
C PBF C C C PBF C
21 2 2 3 2 14, 5 3
C ⫽ caliber variation pattern; F ⫽ female; M ⫽ male; PBF ⫽ pulsatile blood flow pattern; PV ⫽ pulsatile vessel. *Observable duration of the pulsation of PV on ICGA after dye injection. † Time interval between the appearance and the disappearance of pulsation on ICGA. ‡ After laser photocoagulation. § After sub-Tenon triamcinolone acetonide.
the pulsatile movement of 2 PVs was observed for at least 6 to 15 months and disappeared spontaneously. The pulsatile movement may disappear without treatment in some cases, with or without resolution of the reddish-orange nodules. Thus, pulsatile PVs are not always associated with massive subretinal hemorrhage, as suggested by some investigators.20,21 The pulsatile PVs appeared in the late choroidal arteriolar filling phase or early choroidal venular filling phase, and some were observable even during the first 15 minutes after ICG dye injection. The pulsatile movement of PVs may be classified into 2 patterns on ICGA in the present study: (1) a rhythmic movement of the vessel wall with apparent vasodilation and vasoconstriction (caliber variation pattern) and (2) a pulsatile blood flow in a tortuous, relatively narrow choroidal vessel (pulsatile blood flow pattern). In the latter pattern, the blood flow in a narrowed or constricted region of the tortuous choroidal vessel exhibited higher, rhythmic velocity and slowing of blood flow distal to the narrowed or constricted region. These 2 patterns may represent a single phenomenon viewed from different angles. We speculate that the vasoarchitecture is such that a venule is narrowed or constricted by a crossing arteriole and is dilated at the poststenotic portion, resulting in hyperperme-
ability. These features suggest focal venous stasis. In this setting, the choroidal venule might be susceptible to the pulse wave, with the stenotic region exhibiting greater blood flow (i.e., velocity) and the poststenotic region exhibiting caliber variation. To our knowledge, PCV is the only choroidal vascular disease in which such pulsatile movements in blood vessels have been observed on ICGA. Pulsation has not been well documented in either physiologic or pathologic choroidal vessels. Bischoff et al23 examined the choroidal circulation of 173 patients using scanning laser ICGA and found a choroidal pulsation in the macular region in 94 (54%): 84% of these patients exhibited this pulsation during the first few seconds after the inflow of ICG, and this was believed to be a physiological phenomenon. Sixteen of 94 cases revealed a localized pulsation of longer duration (10 –15 seconds) with back and forth movements of dye in 1 or a few choroidal veins. This pulsation with a longer duration was regarded as abnormal and possibly reflected phasic pressure changes in choroidal veins with low flow or direct transmission of the pulsation from an arteriole to a venule (arteriovenous shunt or arteriovenous crossing). The abnormal inflow (back and forth movements) in the choroidal vein of patient 5 (which occurred 10 weeks before the appearance of pulsatile move-
Figure 1. A, Color fundus photograph of patient 1 showing several reddish-orange nodules in the macula with pigmentary change, right eye. Arrow indicates the same site as the arrows in Fig 2B, C. B and C, Indocyanine green angiograms taken 60 and 63 seconds after dye injection indicating network vessels with several beaded polypoidal lesions in the macula. Note the change in the caliber of the polypoidal vessel (arrows) between the 2 frames. The pulsatile vessel shows a rhythmic movement such that its caliber appeared (B) dilated and (C) constricted (caliber variation pattern). See also video 1 (available at http://aaojournal.org).
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Okubo et al 䡠 Pulsatile Polypoidal Vessels in PCV Patients with Pulsatile Polypoidal Vessel Onset of Pulsation
Disappearance of Pulsation
Period of Pulsation (mos)†
Final Best-Corrected Visual Acuity
Follow-up period (mos)
General Condition
At first examination During follow-up At first examination During follow-up During follow-up At first examination At first examination
Unknown Yes Yes‡ No Yes Yes Yes§
Unknown 5 3 3 1 6, 15 2
20/1000 20/40 20/20 20/63 20/500 20/30 20/20
51 36 28 24 23 19 15
None None Arrhythmia Hypertension Hypercholesterolemia Hypertensive cardiac disease None
ments in a PV) seems to represent this type of pulsatile inflow. In contrast to the pulsatile choroidal inflow described by Bischoff et al, the pulsatile movement of PVs in the present study appeared in the late choroidal arteriolar filling phase or the early venular filling phase, and some were observable even in the late choroidal venous filling phase. This implies that the pulsatile movement of PV does not reflect a mere physiologic phenomenon. An unusual pulsation is known to occur in various tissues.24 –29 Some arterial aneurysms, including retinal macroaneurysms show a pulsatile movement.24 –26 Veins have also exhibited pulsatile movement under normal and some
unusual conditions: jugular venous pulse, pulsatile varicose veins,27,28 pulsatile femoral veins29 resulting from a retrograde pulsatile flow caused by elevated right-atrial pressure; arteriovenous shunt (AVS) and a vein neighboring an artery, in which the arteriolar pulse wave is directly transmitted to the vein. Considering the phase of its appearance and the long duration on ICGA, the pulsatile movement of PV observed in this study seems to relate to an AVS or neighboring arteriovenous crossing. In the retina, Tanaka et al30 reported that AVS at the arteriovenous crossing could occur in retinal vascular diseases such as branch retinal vein occlusion and
Figure 2. A and B, Sequential indocyanine green angiograms (ICGAs) of patient 5 taken (A) 16 and (B) 18 seconds after dye injection (at presentation) indicating a beaded vessel (arrowhead) temporal to the fovea and an abnormal pulsatile inflow (back and forth movements) in a choroidal vein (arrows) inferior to the superotemporal vascular arcade. Note the change in the width of the dye flow (arrows) in the choroidal vein between the 2 frames. C, Fundus photograph 10 weeks later showing a reddish-orange lesion (arrowhead) associated with hard exudates, subretinal hemorrhage, and serous retinal detachment in the macula. D, Early choroidal venular filling phase from ICGA taken on the same day as in C showing a pulsatile polypoidal vessel. E, Schematic representation of the choroidal vessels within the outlined portion in Fig 2D. Yellow polypoidal structure indicates a pulsatile vessel with rhythmic variations in the caliber. Red arrows indicate abnormal pulsatile inflow (back and forth movements) in the choroidal vein.
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Figure 3. A, Color fundus photograph of patient 6 reveals 2 reddish-orange nodules at the center of the fovea (black arrowhead) and inferonasal to the fovea (white arrowhead), accompanied by shallow neurosensory detachment in the macular region, right eye. B–E, Sequential indocyanine green angiograms of the same subject taken (B) 32 seconds, (C) 36 seconds, (D) 51 seconds, and (E) 61 seconds after dye injection showing 2 polypoidal vessels (arrows) corresponding to the reddish-orange nodules. Note the time taken after dye injection of each frame and the speed of the dye filling after passing a narrow portion of the tortuous choroidal vessel at the center of the fovea. F, Schematic representation of the blood flow in the polypoidal vessel at the center of the fovea. The blood flow within a narrow portion (curved red arrow) of the tortuous vessel shows higher velocity, while the dye filling within the post-stenotic portion (curved green arrow) proceeds slowly (pulsatile blood flow pattern). See also video 2 (available at http://aaojournal.org).
retinal artery occlusion. The same authors stated that the vessels, particularly veins at an arteriovenous crossing where the artery and the vein have a common adventitia, show vasodilation and hyperpermeability in response to a decrease in perfusion pressure, and direct inflow from artery to vein occurs when vasodilation and hyperpermeability are prolonged. The filling delay of the dye, which was found most prominently in the pulsatile flow pattern in the present study, seems to indicate stasis peripheral to the PV. The abnormal inflow (back and forth movement) of the choroidal vessel near the PV that became pulsatile 10 weeks later in patient 5 seems to reflect phasic pressure changes in low-flow choroidal veins, as suggested by Bischoff et al.23 These findings imply that focal venous stasis could exist followed by vasodilation and hyperpermeability in the choroid. We could not confirm the positional relationship between pulsatile PVs and arteriovenous crossings in the present study, because numerous choroidal vessels at different levels appear simultaneously on ICGA. However, previous clinicopathologic studies16 –18 have shown a close relationship between pathologic choroidal venules and arterioles in PCV: a tortuous, aneurysmally dilated choroidal venule manifesting hyperpermeability and an arteriole showing sclerosis had common adventitia, apparently forming an arteriovenous crossing. In these situations, AVS also may develop as seen in the retina.30 In the choroid, arterioles and venules frequently intersect, particularly within the macular and peripapillary areas, and the choroidal ves-
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sels in these areas are tortuous.31–35 In addition, vascular tortuousness increases with arteriosclerosis. All of these features may be associated with AVS. Herein, we report the features of pulsatile PVs in PCV. Although we could not identify the exact mechanism of this phenomenon, it is possible that pulsatile PVs reflect sites of AVS or arteriovenous crossing in the choroidal vasculature as suggested by our ICGA findings. Further elucidation of this phenomenon of pulsatile movement in PVs might be helpful in understanding the pathogenesis of PCV. Acknowledgments. The authors thank Dr Teruto Hashiguchi of the Department of Laboratory and Vascular Medicine and Dr Masaaki Miyata of the Department of Cardiovascular, Respiratory and Metabolic Medicine in Kagoshima University Graduate School of Medical and Dental Sciences for helpful discussion to interpret the pulsatile blood flow.
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