From the Department of Ophthalmology and Visual Sciences (SA, SH, HM, EK, HY), Yamagata University School of Medicine; the Department of Ocular Cellular Engineering (TY), Yamagata University Hospital; and Yamagata Shinoda General Hospital (KS), Yamagata, Japan.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Sachi Abe, Yamagata University 2-2-2 Iidanishi, Yamagata, 990-9585, Japan.
Polypoidal choroidal vasculopathy (PCV) is a type of age-related macular degeneration (AMD) disease.1 The main lesions are abnormal networks of blood vessels arising from choroidal vessels, which are dilated at their ends.1–3 The causes of PCV have not been fully elucidated, but possible causes are choroidal neovascularization (CNV) or abnormality of existing choroidal vessels.3 Diagnosis is based on orange-red elevated lesions on fundus examination,3,4 corresponding to “polypoidal lesion” on indocyanine green angiography (IA).1–4 Abnormal blood vessel networks and pigment epithelium detachment (PED) are frequently detected with polypoidal lesions.5–7 It is difficult to obtain three-dimensional images showing correlation between abnormal blood vessel networks and polypoidal lesions in situ using cross-sectional images by optical coherence tomography (OCT) or C-scan.8–10 We report that segmentation analysis of retinal pigment epithelium (RPE) level is useful for observing the 3-dimensional structures and their changes of abnormal blood vessel networks surrounding polypoidal lesions.
Design and Methods
Five eyes of 5 patients with PCV without acute hemorrhagic changes or subretinal proliferative tissue were observed using spectral-domain OCT (Cirrus HD-OCT™, Carl Zeiss; Meditec, Dublin, CA) between April and July 2008. Eyes with and without a history of photodynamic therapy (PDT), laser treatment, or intravitreal injection were included.
Diagnostic criteria for PCV were similar to those used by the Japanese Study Group for PCV.4 Observations were made using slit-lamp biomicroscopy, fundus color photography, fluorescein fundus angiography (FA), and indocyanine green angiography (IA). The diagnosis was based on findings of polypoidal lesions observed by IA.4 Polypoidal lesions are visualized by funduscopy as orange-red sub-retinal lesions. Cases with all these features were designated as “definite” cases. The present study included probable cases with no orange-red lesions but with polypoidal lesions on IA.4 An occult lesion on FA was used to estimate the extent of spread of abnormal blood-vessel networks.3 The axial resolution was 5 μm and scanning speed was 27 kA scans/s for Cirrus HD-OCT (hereafter denoted as “spectral-domain OCT”). Tomogram and segmentation analysis with spectral-domain OCT were used to compare tomograms and three-dimensional features of PCV lesions.11
We selected five cases without hemorrhage, exudative lesions, or classic CNV under the retina to observe the association between polypoidal lesions and abnormal blood-vessel networks. The clinical records of the selected five subjects (Table) were as described below.
Table: List of Clinical Records and Ocular Findings of Subjects
Case 1 (Fig. 1): A 54-year-old man with a history of diabetes and hypertension was referred to our hospital on June 17, 2008 because of an abnormal finding in the macular lesion of the left eye. The best-corrected visual acuity (VA) for the left eye was 1.2 (20/16). On January 5, 2009, we detected enlargement of hemorrhagic PED by fundus examination. His visual acuity remained unchanged.
Figure 1. (A) Color fundus photograph. Fundus Examination Shows Four Sites of Orange-red Sub-Retinal and Sub-RPE Lesions (Polyp Lesions of 1/2 Disc Diameter Size, Indicated as a, b, c, d) and Hemorrhagic PED Lesions Adjacent to Polyp Lesions in the Macular Area of the Left Eye. (B) Fluorescein Angiography (FA) Findings Show an Aneurysm-Shaped Hyperfluorescence, Possibly Corresponding to Orange-red Subretinal Lesions (a, b, c, d), with Fluorescein Block Corresponding to Hemorrhagic PED. Mesh-Shaped Hyperfluorescence [arrow] is also Observed in the Macular Area and Corresponds to Abnormal Blood-Vessel Networks. (C) ICG Angiography (IA) Findings of the Left Eye Show polyp lesions (a, b, c, d). Abnormal choroidal vessels (irregular lumen and dilation, tortuosity) are found in areas considered to be abnormal blood-vessel networks on FA. (D) Tomography by OCT. Irregularity of RPE and the double-layer (DL) sign corresponding to abnormal blood-vessel networks in FA and IA are noted. Steep protrusions corresponding to polyp lesions [P] and the surrounding hemorrhagic PED lesion are observed. (E) An area of size 200 × 200 scan in the macula area is analyzed by segmentation of OCT. (F) Segmentation analysis findings. ILM-RPE and ILM show only protruded lesions corresponding to the polypoidal lesion and other lesions. The segmentation analysis of RPE shows uneven images corresponding to mesh-shaped protrusions formed by abnormal blood-vessel networks on FA and IA adjacent to polyp lesions (a, b, c, d), and the double-layer sign [arrow]. (G) Color fundus photograph of case 1 on January 5, 2009, revealing enlargement of hemorrhagic PED. (H) Segmentation analysis of RPE on January 5, 2009 shows the change in shapes by the segmentation analysis of RPE. The segmentation image reveals that the PED surrounding A, B, and C polyp lesion is enlarged, and that the PED surrounding the D polyp lesion is flattened and extended.
Cases 2 (Fig. 2A): A 75-year-old man visited our hospital on April 15, 2008 due to decrease of VA in the right eye. Best-corrected VA of the right eye was 0.15 (20/125).
Figure 2. A-IA, A-OCT, A-Segmentation: Case 2. IA Shows a Polyp Lesion (a), and No Surrounding Abnormal Blood-Vessel Network. Tomography by OCT Shows a Polypoidal Lesion (a) Surrounding Irregular RPE, and the Double-Layer Sign. The Segmentation Analysis Shows a Localized, Steep, Protruded Polypoidal Lesion, and Surrounding Short Uneven Area Corresponding to an Abnormal Blood-Vessel Network.
Case 3 (Fig. 2B): A 65-year-old man first visited our hospital on July 17, 2008. His primary complaint was warped vision in the right eye. Best corrected VA of the right eye was 0.2 (20/100). We detected reduction of his PED after PDT on September 22, 2008. His VA improved from 0.2 (20/100) to 0.3 (20/63).
Case 4 (Fig. 2C): A 69-year-old man visited our hospital on April 22, 2008 with a primary complaint of decreased VA of the left eye. Best-corrected VA of the left eye was 0.5.
Case 5 (Fig. 2D): A 77-year-old woman visited our hospital on March 11, 2008. Best corrected VA of the right eye was 0.2. He underwent PDT on April 17, 2008, and recurrence was noted.
Cases 1, 2, and 4 did not undergo any treatments during the follow-up period.
Case 1: Fundus examination showed four sites of orange-red subretinal lesions and sub-retinal pigment epithelium (RPE) lesions, as well as hemorrhagic PED lesions adjacent to the polypoidal lesions in the macular area in the left eye. These findings were confirmed by FA and IA on June 19, 2007 (Fig. 1A, B). FA and IA showed polypoidal lesion-shaped hyperfluorescence, which possibly corresponded to orange-red subretinal lesions (Figs. 1B, C, and A–D). The fluorescein block findings were considered to be hemorrhagic PED (Fig. 1B). A mesh-shaped hyperfluorescence was also observed in the macular area, and was considered to be an abnormal blood-vessel network (Figs. 1B and C). RPE atrophy over the polypoidal lesions made abnormal blood-vessel networks visible (Fig. 1B).
On June 23, 2008, spectral-domain OCT revealed polypoidal lesions and hemorrhagic PED lesions in the macular area of the left eye (Fig. 1D). Irregularity of RPE was detected as two separate, highly reflective RPE lines. The findings were reported as a double-layer sign (DL in Fig. 1D) that covers abnormal blood-vessel networks observed by FA and IA.9 Acutely protruding RPE was observed over an aneurysm-shaped hyperfluorescence (polyp lesions; P) and surrounding hemorrhagic PED lesions were also noted by FA and IA. A scanned area of the macula (200 × 200) was analyzed by segmentation using spectral-domain OCT (Fig. 1E). Segmentation of the internal limiting membrane (ILM)–RPE and the ILM showed only protruding lesions corresponding to the polypoidal lesion and other lesions. Segmentation analysis of RPE showed uneven images corresponding to mesh-shaped protrusions formed by abnormal blood-vessel networks on FA and IA adjacent to the polyp lesions (Figs. 1F and A–D) and double-layer sign (Figs. 1D and F). On January 5, 2009, we observed enlargement of hemorrhagic PED by fundus examination (Fig. 1G). The segmentation image revealed that the PED surrounding A, B, and C polyp lesions was enlarged, and the PED surrounding the D polyp lesion was flattened and extended. These three-dimensional changes were observed only by segmentation images (Fig. 1H).
Three-dimensional images of lesions corresponding to aneurysm-shaped lesions and abnormal blood-vessel networks in the other 4 patients were observed by segmentation analysis (Figs. 2, 4, and 5). The mound-like lesion in case 3 flattened after PDT, which was detected clearly by segmentation analysis (Fig. 3).
Figure 4. C-IA, C-OCT, C-Segmentation: Case 4. IA Shows Polypoidal Aneurysms (c) and Surrounding Abnormal Blood-Vessel Networks. Tomography by OCT Shows Polypoidal Lesions, Surrounding Irregular Findings of RPE (Double-Layer Signs) and Serous Retinal Detachment; PED is not Observed. The Segmentation Analysis Shows a Localized, Steep, Protruded Polypoidal Lesion, and Surrounding Uneven Area Corresponding to Abnormal Blood-Vessel Networks.
Figure 5. D-IA, D-OCT, D-Segmentation: Case 5. IA Shows a Polypoidal Lesion (d) and Surrounding Abnormal Blood-Vessel Networks. Tomography by OCT Shows a Polypoidal Lesion and Surrounding Irregular Findings of RPE, and Serous Retinal Detachment. Segmentation Shows a Localized, Steep, Protruded Polypoidal Lesion and Surrounding Uneven Area Corresponding to Abnormal Blood-Vessel Networks.
Figure 3. B-IA, B-OCT, B-Segmentation: Case 3. IA Shows Polypoidal Aneurysms (b) and Surrounding Abnormal Blood-Vessel Networks. Tomography by OCT Shows a Polypoidal Lesion. The Segmentation Analysis Shows Uneven Areas, Corresponding to Abnormal Blood-Vessel Networks and PED. B’-IA, B’-Segmentation: Case 3 After Photodynamic Therapy (PDT). The Polypoidal Lesion Cannot be Detected After PDT. By Segmentation, the Mound-Like PED Flattens After PDT.
According to previous reports, the basic PCV lesions are branched abnormal blood-vessel networks stemming from choroidal vessels, which are dilated at their ends and have polypoidal foci.1–3 Two proposed causes of polypoidal lesions are a form of CNV13,14 or an abnormality of existing choroidal vessels.15,16 FA and IA (particularly the latter) are useful for observing and analyzing the pathological status of vessel lesions.1–4 IA cannot necessarily detect abnormal blood-vessel networks or CNV. In the present study of PCV patients, segmentation analysis of the RPE level showed polypoidal lesions in which the RPE protruded and uneven images that possibly corresponded to PED and a mesh structure. The protrusion was reported in previous studies using tomography by OCT,8 and polypoidal lesions were also observed by segmentation analysis in the present study. The uneven images corresponded to the area of the double-layer sign9 and may be considered as abnormal blood-vessel networks. Our observations of Case 1 (Fig. 1F) confirmed that the area of the double-layer sign corresponded to the observed blood vessel networks due to atrophy of RPE observed on FA and IA, and the observed areas of uneven images by segmentation analysis corresponded to the abnormal networks beneath RPE.8,9 Segmentation images also showed polypoidal lesions at the site of possible abnormal blood-vessel networks and the location of abnormal blood-vessel networks at the level of the choriocapillaris just beneath RPE as well as polypoidal lesions. The clinical course that resulted in atrophy in Case 1 is unknown. Active PCV with hemorrhage may coincide with the geographic atrophy of late age-related macular degeneration.17 In the remaining PCV cases (Cases 2 to 5), observation of the areas corresponding to polypoidal lesions and abnormal blood-vessel networks led to segmentation images of RPE with possible abnormal blood-vessel networks surrounding the area corresponding to polypoidal lesions. On spectral-domain OCT, double-layer signs were always present at sites corresponding to abnormal blood-vessel networks.9
The clinical significance of our observations is that the segmentation images obtained by spectral-domain OCT provided the three-dimensional structure of the abnormal blood-vessel networks just beneath RPE, corresponding to occult lesions by FA or the double-layer signs observed by OCT in PCV cases. Our observations provide information that will be useful in estimating the extent of spread of polypoidal lesions and abnormal blood-vessel networks, particularly in the early stage of PCV before hemorrhage or classic lesions. Even in a patient without abnormal blood-vessel networks detected by IA (Case 2), the occult lesion was detected on FA, the double-layer sign was observed by OCT, and segmentation images showed unevenness of RPE surrounding the abnormal blood-vessel networks around the polypoidal lesions. In addition, we could detect changed pathological findings including the changes of shapes and extend PEDs (Cases 1 and 3) from the “bird’s-eye” view. In Case 1, the hemorrhagic PED adjacent to polyp lesion D was observed to be enlarged by funduscopic examination, but the segmentation analysis revealed that the mound-like lesion was flattened and extended. These changes were observed only by the segmentation analysis. These segmentation findings provide information that will be useful for estimating the extent of lesions.
In conclusion, segmentation images obtained by spectral-domain OCT (Cirrus HD-OCT™) can be used to obtain the three-dimensional structures of polyp lesions and surrounding abnormal blood-vessel networks located beneath RPE. Changes in PCV-related lesions were also observed, for example, enlargement of hemorrhagic PED and the reduction of PED after PDT. The segmentation analysis is useful to observe PCV lesions from the bird’s eye view.
- Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy. Retina. 1990;10:1–8. doi:10.1097/00006982-199001010-00001 [CrossRef]
- Uyama M, Wada M, Matsumura M, et al. Polypoidal choroidal vasculopathy:natural history. Am J Ophthalmol. 2002;133:639–648. doi:10.1016/S0002-9394(02)01404-6 [CrossRef]
- Ciardella AP, Donsoff IM, Yannuzzi LA, et al. Polypoidal choroidal vasculopathy. Surv Ophthalmol. 2004; 49:25–37. doi:10.1016/j.survophthal.2003.10.007 [CrossRef]
- Japanese Study Group of Polypoidal Choroidal Vasculopathy. Criteria for diagnosis of polypoidal choroidal vasculopathy. Jpn J Ophthalmol. 2005;109:417–427.
- Tsujikawa A, Sasahara M, Yoshimura N, et al. Pigment epithelial detachment in polypoidal choroidal vasculopathy. Am J Ophthalmol. 2007;143:102–111. doi:10.1016/j.ajo.2006.08.025 [CrossRef]
- Spaide RF, Yannuzzi LA, Orlach DA, et al. Indocyanine green video-angiography of idiopathic polypoidal choroidal vasculopathy, Retina. 1995; 15:100–110. doi:10.1097/00006982-199515020-00003 [CrossRef]
- Sasahara M, Tsujikawa A, Yoshimura N, et al. Polypoidal choroidal vasculopathy with choroidal vascular hyperpermeability. Am J Ophthalmol. 2006;142:601–607. doi:10.1016/j.ajo.2006.05.051 [CrossRef]
- Iijima H, Iida T, Tsukahara S, et al. Optical coherence tomography of orange-red subretinal lesions in eyes with idiopathic polypoidal choroidal vasculopathy. Am J Ophthalmol. 2000; 129:21–26. doi:10.1016/S0002-9394(99)00253-6 [CrossRef]
- Sato T, Kishi S, Mukai R, et al. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina. 2007; 27:589–594. doi:10.1097/01.iae.0000249386.63482.05 [CrossRef]
- Saito M, Iida T, Nagayama D. Cross-sectional and en face optical coherence tomographic features of polypoidal choroidal vasculopathy. Retina. 2008; 28:459–464. doi:10.1097/IAE.0b013e318156db60 [CrossRef]
- Ahlers C, Simader C, Schmidt-Erfurth U, et al. Automatic segmentation in 3-dimensional analysis of fibrovascular pigment epithelial detachment using high-definition optical coherence tomography. Br J Opthalmol. 2008;92;197–203. doi:10.1136/bjo.2007.120956 [CrossRef]
- Gomi F, Tano Y. Polypoidal choroidal vasculopathy and treatment. Curr Opin Ophthalmol. 2008; 19:208–212. doi:10.1097/ICU.0b013e3282fb7c33 [CrossRef]
- Otsuji T, Takahashi K, Uyama M, et al. Optical coherence tomographic findings of idiopathic polypoidal choroidal vasculopathy. Ophthalmic Surg Lasers. 2000;31:210–214.
- Lafaut BA, Aisenbrey S, Heimann K, et al. Polypoidal choroidal vasculopathy pattern in age-related macular degeneration: a clinicopathologic correlation. Retina. 2000;20:650–654. doi:10.1097/00006982-200011000-00010 [CrossRef]
- Okubo A, Sameshima M, Ohba M, et al. Clinicopathological correlation of polypoidal choroidalvasculopathy revealed by ultrastructural study. Br J Ophthalmol. 2002 ;86:1093–1098. doi:10.1136/bjo.86.10.1093 [CrossRef]
- Yuzawa M, Mori R, Kawamura A. The origins of polypoidal choroidal vasculopathy. Br J Ophthalmol. 2005;89:602–607. doi:10.1136/bjo.2004.049296 [CrossRef]
- Bird AC, Bressler NM, Bressler SB. An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol. 1995; 39:367–374. doi:10.1016/S0039-6257(05)80092-X [CrossRef]
List of Clinical Records and Ocular Findings of Subjects
|Age||Sex||Eye||O-R Lesion||B||P||N||P Leakage||WD||GH at Network||DL||RPE Irregular||PED||SRD|