Polypoidal Choroidal Vasculopathy Masquerading as Neovascular Age-Related Macular Degeneration Refractory to Ranibizumab

Stangos, Alexandros N.; Gandhi, Jagdeep Singh; Nair-Sahni, Jayashree; Heimann, Heinrich; Pournaras, Constantin J.; Harding, Simon

doi:10.1016/j.ajo.2010.05.035

Cited by 94 publications

(67 citation statements)

References 19 publications

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“…Our data suggest that (i) increased HTRA1 can lead to up-regulation of VEGF in the RPE/choroid of hHTRA1 + mice, and (ii) VEGF elevation is not sufficient to induce PCV although it is critical for CNV pathogenesis (see Discussion). Our results explain the limited effect of anti-VEGF therapy in treating PCV (40)(41)(42)(43).…”

Section: Resultsmentioning

confidence: 65%

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.

131

139

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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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Section: Resultsmentioning

confidence: 65%

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.

131

139

View full text Add to dashboard Cite

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“…Overall, the effects of IVR monotherapy against PCV are currently contentious, and no consensus has been reached to date. Some studies reported that the polypoidal lesions of PCV were barely resolved by anti-VEGF monotherapy, which might explain the limited efficacy of IVR against PCV [138,139,140]. However, Song et al [141] reported that IVR without PDT for PCV in Korean patients resulted in significant visual and anatomical improvements over a 1-year follow-up period, and other reports suggested that the disappearance of the polypoidal lesions occurred at a high rate in PCV cases after anti-VEGF monotherapy [74,142,143].…”

Section: Response To Treatmentmentioning

confidence: 99%

Polypoidal Choroidal Vasculopathy: Clinical Features and Genetic Predisposition

2013

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Polypoidal choroidal vasculopathy (PCV) is currently recognized as a phenotype of age-related macular degeneration (AMD). PCV is believed to be a type of choroidal neovascularization, although some cases of PCV show a distinct vascular abnormality of the choroidal vessels. PCV often shows several unique clinical manifestations which are apparently different from typical neovascular AMD (tAMD). In addition, the natural course and response to treatment are often different between tAMD and PCV. Moreover, recent genetic studies suggested a possible difference in the genetic susceptibility to disease between tAMD and PCV, as well as the existence of heterogeneity among PCV cases. In viewing the accumulation of knowledge about PCV, we have summarized the recent literature regarding PCV in this review article to improve the understanding of this clinical entity including possible susceptibility genes. We will also discuss the optimal treatment strategies for PCV in accordance with the results of recent clinical and genetic studies.

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“…[12][13][14][15][16][17][18] However, some eyes with exudative AMD are refractory to repeated anti-VEGF therapy. 19,20 Clinicians sometimes see cases of typical AMD with a large lesion that shows a poor response to treatment and that shows progression, which results in a poor visual prognosis. When we performed IA on such AMD cases with large lesions, we sometimes noted knob-like hyperfluorescent lesions at the end of progressing CNV, which resembled the polypoid lesions typically seen in PCV.…”

Section: Introductionmentioning

confidence: 99%

Development of polypoidal lesions in age-related macular degeneration

Tsujikawa

Ojima

Yamashiro

et al. 2011

Eye

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Purpose To investigate the development of polypoidal lesions using indocyanine green angiography (IA) in eyes with typical age-related macular degeneration (AMD). Methods We retrospectively reviewed the medical records of 47 consecutive patients (47 eyes) with typical AMD who had been followed up with IA for at least 2 years. Results At the initial visit, although all eyes showed classic and/or occult choroidal neovascularization (CNV) associated with AMD, no eyes showed polypoidal lesions by IA. However, during follow-up, 13 (27.7%) of the 47 eyes did show polypoidal lesions. All polypoidal lesions developed at the edge of persistent CNV or, more often, at the terminus of recently progressed CNV. Of 12 eyes with a final lesion area 48 disc area, 7 (58.3%) showed newly developed polypoidal lesions. In the eyes with these newly developed polypoidal lesions, the mean area of the vascular lesion had extended significantly from 10.50±7.88 mm 2 to 20.87±10.21 mm 2 during follow-up (P ¼ 0.0018). Conclusion The current observation suggests that IA of active AMD sometimes reveals polypoidal lesions if there is progression of the CNV in the subretinal pigment epithelium space.

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Polypoidal Choroidal Vasculopathy Masquerading as Neovascular Age-Related Macular Degeneration Refractory to Ranibizumab

Cited by 94 publications

References 19 publications

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

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

Polypoidal Choroidal Vasculopathy: Clinical Features and Genetic Predisposition

Development of polypoidal lesions in age-related macular degeneration

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