Akiyuki Kawamura

The origins of polypoidal choroidal vasculopathy.

Background/aim: There are two theories on the pathogenesis of polypoidal choroidal vasculopathy (PCV): variants in choroidal neovascularisation (CNV) and inner choroidal vessel abnormalities. On indocyanine green angiography (IGA) with a video camera system, PCV has a characteristic appearance, but inadequate image quality has made detailed interpretation difficult. This study aims to improve imaging, using confocal scanning laser ophthalmoscopy (SLO), to elucidate the pathogenesis of PCV. Methods: High speed IGA with confocal SLO of 45 eyes (44 patients) showed typical PCV findings of a branching vascular network and polypoidal lesions. Results: Vessels comprising branching networks began to fill simultaneously with the surrounding choroidal arteries in 38 eyes. Small numbers of vessels filling within a branching network, in the arterial and arteriovenous phases of IGA, showed focal dilatation, constriction, and tortuousity. Vessel abnormalities, corresponding to polypoidal lesions, existed within a network in eight eyes and included loops similar in calibre to network vessels, and numerous microaneurysmal dilatations of small vessels. Vessel pulsation was seen in 24 eyes. Conclusion: PCV is caused by inner choroidal vessel abnormalities, not CNV.

Clinicopathologic Findings in Polypoidal Choroidal Vasculopathy

PURPOSE To elucidate the pathogenic mechanism of polypoidal choroidal vasculopathy (PCV) based on histopathologic findings. METHODS Specimens obtained by surgical excision of PCV from five eyes of five patients (mean age, 75.6 +/- 3.1 years) were studied histopathologically. Immunohistochemical studies were also performed to identify CD34, vascular endothelial growth factor (VEGF), CD68, alpha-smooth muscle actin (alpha-SMA) and hypoxia-inducible factor (HIF)-1alpha. RESULTS Hyalinization of choroidal vessels and massive exudation of fibrin and blood plasma were observed in all the specimens of PCV lesions. Some blood vessels were located above the RPE in two of the five eyes. Immunohistochemically, CD68-positive cells were detected around the hyalinized vessels. There were no alpha-SMA-positive cells in the vessels of PCV. CD34 staining showed endothelial discontinuity. Vascular endothelial cells within the PCV specimens were negative for VEGF. HIF-1alpha positive inflammatory cells were located in the stroma of specimens. CONCLUSIONS Hyalinization of choroidal vessels, like arteriosclerosis, is characteristic of PCV.

Indocyanine green angiographic and optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy into two types

Purpose:  We assessed the characteristic indocyanine green angiographic (ICGA) and spectral domain optical coherence tomographic (SD‐OCT) findings of two types of polypoidal choroidal vasculopathy (PCV), distinguishable by different filling patterns on ICGA.

Associations of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotypes with subtypes of polypoidal choroidal vasculopathy.

PURPOSE To clarify whether complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotypes are associated with subtypes of polypoidal choroidal vasculopathy (PCV), such as polypoidal choroidal neovascularization (CNV) and typical PCV. METHODS Two hundred eighty-seven patients were categorized as having polypoidal CNV (85 patients) or typical PCV (202 patients) on the basis of indocyanine green angiographic findings. In total, 277 subjects without age-related macular degeneration (i.e., free of PCV and CNV), served as controls. I62V (rs800292) in the CFH gene and A69S (rs10490924) in the ARMS2 gene were genotyped, and case-control studies were performed in subjects with these PCV subtypes. RESULTS The polypoidal CNV group included no subjects homozygous for the A/A genotype of rs800292, whereas 7% of the typical PCV group had this genotype. Case-control studies of polypoidal CNV and typical PCV showed significant differences in all distributions of rs10490924 between these two groups. In contrast, the distributions of rs10490924 did not differ between the typical PCV and control groups. Logistic regression analysis with adjustment for confounding factors showed the distributions of rs10490924 to differ significantly between the controls and polypoidal CNV cases (P = 2.1 × 10(-10); OR, 10.87). The T/T genotype was significantly more common in the polypoidal CNV than in the typical PCV group (P = 3.6 × 10(-14); OR, 19.61). CONCLUSIONS PCV may be genetically divisible into polypoidal CNV and typical PCV. The rs800292 variant of the CFH gene is a potential marker for typical CNV. The rs10490924 variant of the ARMS2 gene was shown to be associated with polypoidal CNV. Typical PCV was not associated with this variant.

Morphologic findings in acute central serous chorioretinopathy using spectral domain-optical coherence tomography with simultaneous angiography.

Morphologic Findings in Acute Central Serous Chorioretinopathy Using Spectral Domain-Optical Coherence Tomography With Simultaneous Angiography Central serous chorioretinopathy (CSC) is a condition causing local serous neurosensory detachment in the macular region. In the acute stage, fluorescein angiography (FA) shows a focal leak at the level of the retinal pigment epithelium (RPE), and this focal leak gradually expands into the shape of a smokestack or an inkblot pattern. Leaking fluorescein dye pools in the subretinal space.1 Multiple yellowish dot-like precipitates are seen below the serous neurosensory detachment in the macular region2 and within the retinal layer.3 In addition, a grayish-white lesion, apparently a fibrinous exudate, is occasionally present in the subretinal space.4–9 Numerous clinical studies have examined the demographic features, risk factors, clinical manifestations, and clinical course of CSC.10,11 Recent reports have also implicated aging in the onset of CSC.12,13 Gass1 and Fujimoto et al14 described an RPE defect at the edge of or within areas of pigment epithelial detachment (PED) at leakage sites, through which fluid might pass from the sub-RPE into the subretinal space. Fujimoto et al14 examined leakage sites in acute CSC cases using Fourier-domain optical coherence tomography (OCT), but no study of the leakage site using the Spectral domain-OCT (SD-OCT) and confocal scanning laser ophthalmoscopy (cSLO; Spectralis HRA OCT, Heidelberg Engineering, Heidelberg, Germany) has yet to be reported. Spectralis HRA OCT uses as its light source a superluminescent diode that has a peak wavelength of 870 nm. Scanning an object with two different wavelengths allows simultaneous display of the cSLO image and the OCT image of a chosen plane. Therefore, it is possible to visualize the OCT image of a lesion depicted on angiography (FA or indocyanine green angiography [ICGA]) at the same location. The angiographic image of the structure or the lesion depicted on the OCT image can also be observed. By using Spectralis HRA OCT, we performed FA, ICGA, and OCT during the clinical course of acute CSC. We studied in detail the state of the RPE at the leakage point (LP) and the relationships of the LP to both PED and moderately to highly reflective substances.

Indocyanine Green Videoangiographic Findings in Detachment of the Retinal Pigment Epithelium

BACKGROUND Several forms of retinal pigment epithelial detachment have been reported. The authors used indocyanine green (ICG) videoangiography, which is useful to study the choroidal vasculature and Bruch membrane, to study pigment epithelial detachments. METHODS Ninety-eight pigment epithelial detachments in 75 eyes were classified based on the appearance of choroidal neovascular membranes or late phase findings of ICG videoangiography done at the initial examination. The authors also followed the evolution of 51 such detachments not associated with choroidal neovascularization (CNV). RESULTS Sixty-four pigment epithelial detachments without CNV were divided into five groups. Among eyes with pigment epithelial detachments that showed intense hyperfluorescence, all except one of the patients had both eyes involved and had several pigment epithelial detachments, sometimes with exudative retinal detachments. Weak hyperfluorescence was observed more often in younger patients. During follow-up of eyes with pigment epithelial detachments that showed irregular hypofluorescence, a neovascular membrane developed in one eye, microrips developed in four eyes and retinochoroidal folds in one eye. Most eyes that showed irregular hyperfluorescence developed atrophy of the retinal pigment epithelium. In 34 pigment epithelial detachments with CNV, either irregular hypofluorescence or absence of fluorescence was observed in areas that corresponded to the pigment epithelial detachment. CONCLUSION The intense hyperfluorescence is thought to be due to the accumulation of protein-rich fluid within the pigment epithelial detachment. Most pigment epithelial detachments that showed weak fluorescence probably represent variants of central serous choroidopathy. Pigment epithelial detachments that showed irregular hypofluorescence or hyperfluorescence were associated with age-related macular degeneration, and the former was correlated closely with CNV. Close follow-up therefore is recommended for eyes with pigment epithelial detachments that show irregular hypofluorescence.

Detection of morphologic alterations by spectral-domain optical coherence tomography before and after half-dose verteporfin photodynamic therapy in chronic central serous chorioretinopathy.

Purpose: To study the morphologic features of serous retinal detachment, the photoreceptor inner and outer segment junction line, retinal pigment epithelium irregularities, pigment epithelial detachment, and the subfoveal choroid before and after treatment of chronic central serous chorioretinopathy, using spectral-domain optical coherence tomography. Methods: We studied 17 eyes of 17 consecutive patients (all men) with chronic central serous chorioretinopathy. We performed photodynamic therapy (PDT) with half-dose (3 mg/m2) verteporfin. We studied morphologic features using spectral-domain optical coherence tomography before and at 1, 3, 6, and 12 months after PDT. Results: Retinal detachment showed reattachment in 16 of the 17 eyes by 3 months after PDT. The inner and outer segment junction line could be visualized in 13 eyes at 6 months after PDT. Retinal pigment epithelium irregularities were confirmed in all 17 eyes before and during the year after PDT. Pigment epithelial detachment initially disappeared but then recurred in 5 eyes after PDT. Subfoveal highly reflective substances first lessened in intensity but then again became prominent in 2 eyes. Conclusion: The authors identified recurrent pigment epithelial detachment and/or retinal detachment during the 1-year period after PDT. Even if retinal detachment initially disappears, retinal pigment epithelium or choroidal morphologic changes can still develop. The effect of half-dose PDT for chronic central serous chorioretinopathy may thus be temporary.

Surgical excision of neovascularization in retinal angiomatous proliferation

BackgroundWe report the postoperative outcomes of surgical neovascularization excision in patients with retinal angiomatous proliferation (RAP).MethodsNine eyes of eight patients with RAP who underwent surgical excision of neovascularization were studied. Surgical indications were as follows: RAP diagnosed by fluorescein and indocyanine green angiography, foveal or perifoveal neovascularization, preoperative visual acuity of 0.1 or less, Yannuzzi’s stage II with detachment of retinal pigment epithelium (RPE) or stage III, and leakage on late-phase fluorescein angiography. After cataract surgery, vitreous surgery and neovascularization excision were conducted, followed by fluid–air or fluid–gas exchange.ResultsVisual acuity was 0.02–0.1 before surgery and 0.03–0.2 after surgery. Macular hole formation was seen in one eye but did not lead to retinal detachment. In two eyes, subretinal bleeding occurred during excision leading to vitreous bleeding after surgery. Although defects of the RPE and choriocapillaries were observed after surgery, the exudation and bleeding were absorbed.ConclusionsIn stage II RAP cases with RPE detachment, surgical excision maintains constant postoperative visual acuity but results in defects of RPE and choriocapillaris; therefore, other treatment options should be examined. Surgical excision of stage III RAP seems to be promising, as postoperative visual acuity remains stable after neovascularization removal in those advanced pathologic situations.

Correlation of Aging and Segmental Choroidal Thickness Measurement using Swept Source Optical Coherence Tomography in Healthy Eyes

Purpose To assess and compare choroidal thickness changes related to aging, we determined whether changes are due to thinning of the choriocapillaris plus Sattlers (CS) layer and/or the large vessel layer in healthy eyes using swept-source optical coherence tomography (SS-OCT) at a wavelength of 1,050-nm. Methods We studied 115 normal eyes of 115 healthy volunteers, all with refractive errors of less than -6 diopters. All 115 eyes underwent analysis of choroidal thickness at the fovea, the CS layer and the large choroidal vessel layer. In 68 of the 115 eyes, choroidal thickness was determined at five sites (the fovea, and superior, inferior, nasal, and temporal sites) using SS-OCT with an Early Treatment of Diabetic Retinopathy grid scan. Results Total choroidal thicknesses at each of the five sites were related to subject age (P<0.0001). The choroid was thinnest at the nasal site, followed by the temporal, inferior, superior and finally the subfoveal site itself. The total choroidal thickness at the nasal site was significantly less than those at the other four sites (p<0.05). The CS layer showed thinning which correlated with age (P<0.0001). The thickness of the choroidal large vessel layer also decreased with age (p = 0.02). Subfoveal choroidal thickness was calculated as follows: 443.89–2.98×age (μm) (P<0.0001). Conclusion Subfoveal choroidal thickness decreases by 2.98 μm each year. Total choroidal thickness diminishes with age. The CS and large vessel layers of the choroid at the subfovea showed significant decreases, though only the former correlated strongly with age.

Morphologic features of focal choroidal excavation on spectral domain optical coherence tomography with simultaneous angiography.

Purpose: To reveal clinically relevant morphologic findings in patients with focal choroidal excavation (FCE) using enhanced depth imaging optical coherence tomography. Methods: Thirty-one FCE lesions in 29 eyes of 26 patients (21 men, 23 eyes; 5 women, 6 eyes) were studies. In all 26 patients, color fundus photographs were obtained, and fluorescein angiography and indocyanine green angiography with simultaneous enhanced depth imaging optical coherence tomography were performed. Twenty-five eyes also underwent angiographic video recording. Results: Focal choroidal excavation was detected in eyes with typical age-related macular degeneration, central serous chorioretinopathy, polypoidal choroidal vasculopathy, and idiopathic choroidal neovascularization, whereas in 8 eyes, FCE was considered to be idiopathic. Morphologically, FCE lesions were classified into 3 types: cone-shaped, bowl-shaped, and mixed. The cone-shaped type was detected in 17 lesions, bowl-shaped in 8, and mixed in 6, on optical coherence tomography findings. All bowl-shaped and mixed types had retinal pigment epithelial irregularities within the FCE lesion. The cone-shaped type was not observed in eyes with typical age-related macular degeneration. Conclusions: Morphologically, FCE lesions were classified into cone-shaped, bowl-shaped, and mixed types, based on optical coherence tomography findings. Focal choroidal excavation formation may be associated in part with chorioretinal diseases such as age-related macular degeneration and central serous chorioretinopathy, whereas some eyes are considered to have idiopathic FCE.