Clinicopathologic Findings in Polypoidal Choroidal Vasculopathy

Nakashizuka, Hiroyuki; Mitsumata, Masako; Okisaka, Shigekuni; Shimada, Hiroyuki; Kawamura, Akira; Mori, Ryusaburo; Yuzawa, Mitsuko

doi:10.1167/iovs.08-2134

Cited by 192 publications

(170 citation statements)

References 39 publications

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“…Likewise, Kuroiwa et al 23 observed changes mainly in the large choroidal arterioles, showing disruption of inner elastic layer, and deposition of basement membrane-like material and collagen in the vessel wall, suggesting that atherosclerosis of inner choroidal arterioles may be important. Similarly, Nakashizuka et al 24 reported hyalinization of choroidal vasculature, again underpinning the role of atherosclerosis in PCV. In the same study, however, they found no VEGF staining of the vascular endothelium of the polyps, in contrast to previous reports.…”

Section: Pathogenesismentioning

confidence: 84%

Polypoidal choroidal vasculopathy: an angiographic discussion

Lim

Laude

Tan

2010

Eye

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The understanding of polypoidal choroidal vasculopathy has evolved rapidly in the past three decades. The hallmark of the disease is the presence of typical hyperfluorescent nodules in the early phase of indocyanine green angiography. Although the classical clinical presentation is recurrent serosanguinous detachment of the retinal pigment epithelium, it may present with clinical features indistinguishable from exudative age-related macular degeneration secondary to choroidal neovascularization. Some cases may present initially with submacular haemorrhage, but later with features of exudative age-related macular degeneration. Studying the associated network of vessels using confocal scanning laser ophthalmoscopy indocyanine green dynamic angiography revealed in many cases feeder vessels, branching pattern, and leakage similar to choroidal neovascularization. Owing to the overlap of clinical and angiographic features, it may be considered as a vascular subtype of exudative age-related macular degeneration. However, having seemingly better natural history, better response to photodynamic therapy, and incomplete response to antivascular endothelial growth factor therapy suggests that it should be studied as a separate entity from choroidal neovascularization. Combining angio-occlusion of the polyps using photodynamic therapy and antipermeability effect of anti-vascular endothelial growth factor therapy on the branching vascular network may provide a synergistic effect. We await the result of EVEREST trial, a multi-centre randomized controlled trial comparing photodynamic therapy, with or without ranibizumab, with ranibizumab monotherapy.

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Section: Pathogenesismentioning

confidence: 84%

Polypoidal choroidal vasculopathy: an angiographic discussion

Lim

Laude

Tan

2010

Eye

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“…VEGF plays a significant role in the progression of CNV (37), although its role in PCV is controversial (32,33,38,39). We examined the expression of VEGF in the RPE/ choroid of hHTRA1 + mice by Western blotting (Fig.…”

Section: Resultsmentioning

confidence: 99%

Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice

Jones

Kumar

Zhang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly. Wet AMD includes typical choroidal neovascularization (CNV) and polypoidal choroidal vasculopathy (PCV). The etiology and pathogenesis of CNV and PCV are not well understood. Genome-wide association studies have linked a multifunctional serine protease, HTRA1, to AMD. However, the precise role of HTRA1 in AMD remains elusive. By transgenically expressing human HTRA1 in mouse retinal pigment epithelium, we showed that increased HTRA1 induced cardinal features of PCV, including branching networks of choroidal vessels, polypoidal lesions, severe degeneration of the elastic laminae, and tunica media of choroidal vessels. In addition, HTRA1 mice displayed retinal pigment epithelium atrophy and photoreceptor degeneration. Senescent HTRA1 mice developed occult CNV, which likely resulted from the degradation of the elastic lamina of Bruch's membrane and up-regulation of VEGF. Our results indicate that increased HTRA1 is sufficient to cause PCV and is a significant risk factor for CNV.A dvanced age-related macular degeneration (AMD) can be classified into wet AMD and geographic atrophy (1, 2). Wet AMD includes the typical choroidal neovascularization (CNV) and polypoidal choroidal vasculopathy (PCV). CNV is caused by the growth of new blood vessels from the choroid into the subretinal pigment epithelium (RPE) and subretinal spaces, whereas PCV is caused by inner choroidal vessel abnormalities (3). PCV has two key features on indocyanine green angiography (ICGA): polypoidal vascular dilations and a network of branching abnormal choroid vessels (4). Both CNV and PCV can lead to recurrent serous exudation and hemorrhages (5). The etiology and pathogenesis of CNV and PCV are largely unknown.Numerous genetic association studies have shown that chromosome 10q26 is a major candidate region associated with the susceptibility of several types of AMD (6, 7), including PCV (8-10). The linkage peak was refined to two neighboring genes, HTRA1 (11, 12) and ARMS2 (or LOC387715) (13). HTRA1 is a multifunctional serine protease that is ubiquitously expressed in mammalian tissues (14, 15) but ARMS2 is primate-specific, with a proposed function in mitochondria (13, 16), extracellular matrix (17), or as a noncoding RNA (18). Variants in this region are in strong linkage disequilibrium (11-13, 16). There are three major competing hypotheses attributing increased risk of AMD to (i) increased HTRA1 (11, 12), (ii) decreased ARMS2 (16), or (iii) both increased HTRA1 and decreased ARMS2 (19). However, a series of studies on the influence of AMD-associated polymorphisms on the expression of ARMS2 and HTRA1 have yielded widely conflicting results (12,16,(18)(19)(20)(21)(22)(23)(24). As a result, the functional involvement of either HTRA1 or ARMS2 in AMD remains uncertain, despite strong genetic evidence (18,22). To clarify the role of HTRA1 in AMD pathogenesis, we transgenically expressed human HTRA1 in mouse RPE. We showed that increased HTRA1 is ...

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“…These findings suggest that the abnormal choroidal vessels under Bruch's membrane may permit fluid to leak into the sub-pigment epithelial space with the impairment of the membrane in the early phase. 19,22 However, in majority of the cases, the fine vascular network seemed to be present within or above Bruch's membrane, and may permit fluid leakage into the sub-pigment epithelial space. This would then be compatible with the reported location of the PCV network and polyps.…”

Section: Discussionmentioning

confidence: 98%

Characteristics of fine vascular network pattern associated with recurrence of polypoidal choroidal vasculopathy

Oishi

Mandai

Kimakura

et al. 2011

Eye

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Objective To characterize an irregular capillary-like structure in the vascular network of eyes with polypoidal choroidal vasculopathy (PCV), and to determine whether its presence after photodynamic therapy (PDT) can be used to predict the clinical course of PCV. Methods We reviewed the clinical records of 29 eyes of 29 patients with PCV, who underwent PDT and confocal retinal angiographic examinations every 3 months. The images obtained before the PDT were compared with those after the PDT. The correlations between angiography findings and recurrences were evaluated. Results An area of fine, densely packed capillary-like vessels, named the fine vascular network, was identified within the polypoidal vascular network in 25 of 29 cases at the initial examination. The fine vascular network regressed in 23 cases (92%) after the first PDT. Thereafter, the fine vascular network remained or enlarged in 19 eyes, and 17 (84.5%) of these eyes had a recurrence of the polypoidal lesions or had exudative changes. In contrast, recurrences were found in only 2 of 10 (20%) eyes, whose fine network had regressed without a subsequent enlargement (Po0.001 compared with the former group). Conclusions A fine irregular vascular network is present in the majority of eyes with PCV before PDT. Its presence or expansion after PDT was significantly associated with a recurrence of PCV. Thus, we recommend that this network be monitored after treatment to determine whether a polypoidal vascular network will recur.

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Clinicopathologic Findings in Polypoidal Choroidal Vasculopathy

Abstract: Hyalinization of choroidal vessels, like arteriosclerosis, is characteristic of PCV.

Cited by 192 publications

References 39 publications

Polypoidal choroidal vasculopathy: an angiographic discussion

Polypoidal choroidal vasculopathy: an angiographic discussion

Increased expression of multifunctional serine protease, HTRA1, in retinal pigment epithelium induces polypoidal choroidal vasculopathy in mice

Characteristics of fine vascular network pattern associated with recurrence of polypoidal choroidal vasculopathy

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