Polypoidal Choroidal Vasculopathy

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Article initiated by:
Negin Agange, MD
All contributors:
Negin Agange, MD, Vinay A. Shah M.D., Leo A. Kim, MD, PhD, Koushik Tripathy, MD (AIIMS)
Assigned editor:
Leo A. Kim, MD, PhD
Review:
Assigned status Update Pending
 by Leo A. Kim, MD, PhD on March 6, 2025.


Polypoidal choroidal vasculopathy (PCV) is a disease of the choroidal vasculature. It is characterized by serosanguineous pigment epithelial detachments (PEDs) and exudative changes that can commonly lead to subretinal fibrosis. There is evidence that symptomatic patients with PCV can have complete regression without severe vision loss following treatment with photodynamic therapy (PDT) and anti–vascular endothelial growth factor (VEGF) agents.

Disease Entity

Disease

The disease process known now as polypoidal choroidal vasculopathy (PCV) was described by Dr. Lawrence Yannuzzi during a presentation of cases at the Macula Society's annual meeting in 1982.[1] He described patients with subretinal vascular lesions associated with serous and hemorrhagic detachments of the retinal pigment epithelium (RPE).[1][2] The name reflects the appearance of a network of branching choroidal vessels with terminal, polyp-like aneurysmal dilations.

Prevalence and Incidence

While PCV has sometimes been described as a disease present in middle-aged black women,[1][3] it has been established that it occurs in both sexes and in all races. It is most commonly diagnosed in patients between age 50 and 65 years. Several studies have assessed the incidence and prevalence of PCV among Asian populations; as well, in Japan higher prevalence rates are seen in patients with presumed age-related macular degeneration (AMD).[3][4][5][6][7][8][9][10]

Etiology and Pathophysiology

The etiology and pathophysiology of PCV are not clearly understood. It has been proposed that the choroidal vasculature has a propensity for dilation and aneurysmal formation.[5][11] Gross specimens are described in the literature for their histopathologic findings; Uyama et al described large vascular channels in their early pathologic state, which has also been observed by other researchers.[2]

Signs/Symptoms

Common visual complaints can include blurred vision, central or paracentral scotoma, and dim vision in the affected eye.

Primary Prevention

Currently, there is no mechanism for primary PCV prevention. Given more research in genetic markers, there may be a time when the risk of developing PCV can be better estimated and treatment can be tailored to individual patient needs.

Diagnosis

Physical Examination

A thorough history and dilated fundus exam are the first steps in diagnosis. On fundus examinations, orange-reddish bulb-like lesions can be seen budding from the choroid into the subretinal space. These lesions can be associated with recurrent and significant hemorrhagic and exudative detachments of the retina and the RPE. Hard exudates are also common. On occasion, patients may present with breakthrough vitreous hemorrhage.

Clinical Diagnosis

The best technique available for differentiating PCV from other types of neovascularization is indocyanine green angiography (ICGA).[12] The ICG molecule is excited by the absorption of infrared light in the range of 790 to 805 nm. The intravascular retention of the ICG molecule allows for better resolution of the choroidal vasculature. Fluorescein angiography (FA) is not as useful because it lacks the same resolution of the choroidal vasculature as ICGA; however, it is able to show large polypoidal changes.

Clinical appearance, findings from ICGA and FA (the latter in certain cases, and high-resolution optical coherence tomography (OCT) imaging assist in making a diagnosis of PCV (Figures 1–3).

.ICGA of polyps in the choroidal vasculature. Image courtesy of Dr. Gelareh Abedi.

Figure 1. ICGA image of polyps in the choroidal vasculature (courtesy of Dr. Gelareh Abedi).

Figure 2. Spectral domain OCT of left macula of patient with suspected PCV.

Figure 2. Spectral-domain OCT image of the left macula of a patient with suspected PCV.

Figure 3. Wide field Optos® of left eye with fluorescein angiography at 22s, 1:45s, and 8:11s demonstrating multiple areas of hemorrhages and serous retinal detachments.

Figure 3. Widefield image of the left eye with FA at 22 seconds, 1:45 minutes, and 8:11 minutes, demonstrating multiple areas of hemorrhages and serous retinal detachments.

Diagnostic Procedures

Fluorescein Angiography (FA)

Seen on FA, PCV lesions resemble occult choroidal neovascular membrane lesions; when submacular, they can be mistaken for AMD. A peripheral notch at the margin of a serous PED may give a clue to the location of the polyp. Retinal pigment epithelium atrophy is manifested as window defects. Subretinal hemorrhage or subretinal pigment epithelial hemorrhage gives block fluorescence. FA also helps to rule out other differentials, including choroidal neovascularization, microaneurysms, and retinal angiomatous proliferans.

Indocyanine Green Angiography (ICGA)

Given its ability to highlight the choroidal vasculature, ICGA is the standard tool for diagnosing polypoidal lesions. On ICGA, the branching network of PCV is easily seen. The polyps present as focal hyperfluorescent spots. In later stages, reversal pattern of dye is seen, with the center of the lesion becoming hypofluorescent and surrounding areas becoming hyperfluorescent. Finally, in the very last stage, there is “wash-out” of the lesion that is seen in nonleaking PCV lesions.[13]

The EVEREST Study Group developed a diagnosis protocol for PCV, based on hyperfluorescence shown on early subretinal ICGA (appearing within the first 5 minutes of ICG dye injection) and at least one of the following diagnostic criteria:[14]

  • Nodular (elevated) appearance of the polyp on stereoscopic viewing
  • Hypofluorescent halo around the nodule
  • Abnormal vascular channel(s) supplying the polyps
  • Pulsatile filling of polyps
  • Orange subretinal nodules corresponding to the hyperfluorescent area on ICGA
  • Extensive submacular hemorrhage (>4 disc areas).

Based on ICGA features, idiopathic PCV (IPCV) can be divided into 2 types:[15][16]

  • Type 1 (polypoidal): polyp(s) with well-defined branching vascular network (BVN; both feeder and draining vessels)
  • Type 2 (typical): polyp(s) with absent BVN (neither feeder not draining vessels)


A typical BVN originates from a feeder vessel and spreads outwards. Polyps are usually located at the periphery. A less-common type of BVN involves interconnecting channels, consisting of crisscrossing choroidal vessels, which supply the polyps. The ICG dye has no specific point of origin or flow direction, unlike with a typical BVN.[14]

Abnormal vascular channels are best seen using dynamic ICGA within 30 seconds; after 1 minute, normal choroidal vessels begin to fill up, so it then becomes difficult to identify abnormal vessels . Dynamic ICGA can help to document the pulsatile filling of polyps. Stereo ICGA pairs images at 1 minute or 3 minutes; this is adequate time to diagnose, locate, and measure the greatest linear dimension of the polyp and abnormal vascular channels.[14] ICGA may also aid in dilation of large choroidal vessels and assessment of choroidal vascular hyperpermeability.

Central serous chorioretinopathy and PCV share a common pachychoroid spectrum, so clinical differentiation between the two may be difficult in clinical settings, though features seen on ICGA and OCT can help aid the clinician in making a correct diagnosis.

Optical Coherence Tomography (OCT)

OCT is not only helpful in identifying subretinal or sub-RPE fluid, it can also delineate polypoidal lesions. These lesions resemble dome-like elevations of RPE with moderate internal reflectivity. In most cases, there is also a highly reflective line just below these lesions consistent with the BVN location.[17] The dual reflective layers are also called the “double-layer sign,” and are seen in 59% of eyes with PCV.[18]

OCT B-scans may show the following:

  • Subretinal fluid
  • Intraretinal cystoid spaces, though typically those are seen less commonly- which may explain surprisingly good visual acuity in some cases[4]
  • Fluid or hemorrhage below PEDs
  • Notched PED—a high PED connected with PED/s of lower height on the sides, with a wavy border and a corrugated or bumpy appearance[19]
  • M-shaped or QRS complex–shaped PEDs
  • Polyps, seen as round or oval structures connected to the outer surface of the PED
  • Double-layer sign at the margin of PED elevation. It may be caused by either separation of the RPE from the Bruch membrane or separation of the Bruch membrane from the choroid[16]


A 2021 article from the Asia-Pacific Ocular Imaging Society PCV Workgroup noted the following: "For the diagnosis of PCV, the combination of 3 OCT-based major criteria (sub-[RPE] ring-like lesion, en face OCT complex RPE elevation, and sharp-peaked PED) achieved an area under the receiver operating characteristic curve of 0.90. Validation of this new scheme in a separate subset of 80 eyes achieved an accuracy of 82%."[20]

OCT C-scan features include:

  • Hematocrit sign: round or oval polyp with blood corpuscles sedimented inferiorly, giving rise to a horizontal level within the polyp between the corpuscles and the serous component of blood[4]
  • Bola sign: multiple polyps connected to each other via abnormal choroidal vascular channels. These are prominently visible in 3D reconstruction using spectral-domain OCT[4] [21]

Laboratory Tests

No specific hematologic or aqueous biomarker testing exists for PCV. In 2014, Park et al proposed a significant relationship between plasma malondialdehyde levels and ARMS2 genetic variants in Korean patients with PCV and neovascular AMD.[22]

Differential Diagnosis

The differential diagnosis for PCV includes other entities that can cause subretinal neovascularization. History and clinical presentation would differentiate PCV from the following limited list of disease processes, including AMD (type 1 or 2), central serous chorioretinopathy, pathological myopia with neovascularization, and choroidal tumors or metastases.

Management

Medical Therapy

Several studies have evaluated treatments for PCV, which include observation, photodynamic therapy, intravitreal anti-VEGF therapy injections, or combination therapy. The EVEREST trial was a multicenter, double-masked study that compared verteporfin photodynamic therapy (PDT) plus the anti-VEGF agent ranibizumab, PDT monotherapy, and ranibizumab monotherapy in 61 Asian patients with symptomatic PCV. The primary end point was complete polyp regression as assessed by ICG. A significantly higher proportion of patients treated with either PDT + ranibizumab or PDT monotherapy had complete polyp regression at month 6 than patients treated with ranibizumab.[23]

Other clinical trials include:

  • The Japanese LAPTOP study, which showed that while treatment with ranibizumab resulted in visual gain from baseline at 24 months, the same effect was not seen after treatment with PDT[24]
  • PLANET study: at 12 months, aflibercept monotherapy was noninferior to aflibercept + PDT in improving visual outcomes[25]
  • EPIC study: at 6 months, aflibercept monotherapy stabilized vision and resulted in resolution of hemorrhagic and exudative complications and in regression of polyps in around 70% of patients[26]

Medical Follow-up

Regardless of choice of treatment, patients should be followed at regular intervals to detect and prevent subretinal/sub-RPE fluid and hemorrhage.

Surgery

There is no current surgical management for PCV. If surgical management is needed, it would be tailored to complications and sequelae of PCV such as breakthrough vitreous hemorrhage. However, laser therapy to polyps and BVN occupying a small area away from the fovea may be considered.

Prognosis

The natural course of PCV depends on the size and extent of serosanguineous PEDs and exudative changes. In a study by Uyama et al, eyes with polypoidal lesion clusters were considered at higher risk of poor prognosis, whereas eyes with solitary lesions had favorable prognosis.[27] Polypoidal lesions are usually located at the margin of the PED. Following the spontaneous resolution of the acute serosanguineous complications, there may be signs of subretinal fibrosis, pigment epithelial hyperplasia, and atrophic degeneration.[18][23],[28]

Depending on the extent of the involved area, the prognosis is generally good. Even in patients with longer chronicity of disease, studies have shown halting of visual decline. There is evidence that symptomatic patients with PCV can have complete regression without severe vision loss with PDT and anti-VEGF treatment.[23]

Acknowledgements

We acknowledge the contributions of Dr. Gelareh Abedi, Dr. C. Armitage Harper III (Third Coast Retina Conference 2013), and Andres Sanchez, photographer for the Department of Ophthalmology at the University of Texas Health Science Center San Antonio.

References

  1. ↑ 1.0 1.1 1.2 Yannuzzi LA. Idiopathic polypoidal choroidal vasculopathy. Presented at: 5th Annual Macula Society Meeting; February 5, 1982; Miami, FL.
  2. ↑ 2.0 2.1 Yannuzzi LA, Sorenson J, Spaide RF, et al. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina. 1990;10(1):1-8.
  3. ↑ 3.0 3.1 Stern RM, Zakov ZN, Zegarra H, Gutman FA. Multiple recurrent serosanguineous retinal pigment epithelial detachments in black women. Am J Ophthalmol. 1985;100(4):560-569.
  4. ↑ 4.0 4.1 4.2 4.3 Imamura Y, Engelbert M, Iida T, et al. Polypoidal choroidal vasculopathy: a review. Surv Ophthalmol, 2010;55(6):501-515.
  5. ↑ 5.0 5.1 Maruko I, Iida T, Saito M, et al. Clinical characteristics of exudative age-related macular degeneration in Japanese patients. Am J Ophthalmol. 2007;144(1):15-22.
  6. ↑ Yannuzzi LA, Ciardella A, Spaide RF, et al. The expanding clinical spectrum of idiopathic polypoidal choroidal vasculopathy. Arch Ophthalmol.1997;115(4):478-485.
  7. ↑ Ciardella AP, Donsoff IM, Huang SJ, et al. Polypoidal choroidal vasculopathy. Surv Ophthalmol. 2004;49(1):25-37.
  8. ↑ Nakashizuka H, Mitsumata M, Okisaka S, et al. Clinicopathologic findings in polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2008;49(11):4729-4737.
  9. ↑ Liu Y, Wen F, Huang S, et al. Subtype lesions of neovascular age-related macular degeneration in Chinese patients. Graefes Arch Clin Exp Ophthalmol. 2007;245(10):1441-1445.
  10. ↑ Sho K, Takahashi K, Yamada H, et al. Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics. Arch Ophthalmol. 2003;121(10):1392-1396.
  11. ↑ Byeon SH, Lee SC, Oh HS, et al. Incidence and clinical patterns of polypoidal choroidal vasculopathy in Korean patients. Jpn J Ophthalmol. 2008;52(1):57-62.
  12. ↑ Spaide RF, Yannuzzi LA, Slakter JS, et al. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina. 1995;15(2):100-110.
  13. ↑ Ciardella AP, Donsoff IM, Huang SJ, et al. Polypoidal choroidal vasculopathy. Surv Ophthalmol. 2004;49(1):25-37.
  14. ↑ 14.0 14.1 14.2 Tan CS, Ngo WK, Chen JP, et al; EVEREST Study Group. EVEREST study report 2: imaging and grading protocol, and baseline characteristics of a randomised controlled trial of polypoidal choroidal vasculopathy. Br J Ophthalmol. 2015;99(5):624-628.
  15. ↑ Kawamura A, Yuzawa M, Mori R, et al. Indocyanine green angiographic and optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy into two types. Acta Ophthalmol. 2013;91(6):e474-e481.
  16. ↑ 16.0 16.1 Honda S, Matsumiya W, Negi A. Polypoidal choroidal vasculopathy: clinical features and genetic predisposition. Ophthalmologica. 2014;231(2):59-74.
  17. ↑ Kamaeda T, Tsujikawa A, Otani A, et al. Polypoidal choroidal vasculopathy examined with en face optical coherence tomography. Clin Exp Ophthalmol. 2007;35(7):596-601.
  18. ↑ 18.0 18.1 Sato T, Kishi S, Watanabe G, et al. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina. 2007;27(5):589-594.
  19. ↑ Alshahrani ST, Al Shamsi HN, Kahtani ES, et al. Spectral-domain optical coherence tomography findings in polypoidal choroidal vasculopathy suggest a type 1 neovascular growth pattern. Clin Ophthalmol. 2014;8:1689-1695.
  20. ↑ Cheung CMG, Lai TYY, Teo K, et al. Polypoidal choroidal vasculopathy: consensus nomenclature and non-ndocyanine green angiograph diagnostic criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup. Ophthalmology. 2021;128(3):443-452.
  21. ↑ Abe S, Yamamoto T, Haneda S, et al. Three-Dimensional Features of Polypoidal Choroidal Vasculopathy Observed by Spectral-Domain OCT. Ophthalmic Surg Lasers Imaging. 2010:1-6.
  22. ↑ Park DH, Shin JP, Kim IT. Association of plasma malondialdehyde with ARMS2 genetic variants and phenotypes in polypoidal choroidal vasculopathy and age-related macular degeneration. Retina. 2014;34(6):1167-1176.
  23. ↑ 23.0 23.1 23.2 Koh A, Lee WK, Chen LJ, et al. EVEREST Study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina. 2012; 32(8):1453-1464.
  24. ↑ Oishi A, Miyamoto N, Mandai M, et al. LAPTOP study: a 24-month trial of verteporfin versus ranibizumab for polypoidal choroidal vasculopathy. Ophthalmology. 2014;121(5):1151-1152.
  25. ↑ Lee WK, Ogura Y, Iida T, et al. Efficacy and safety of intravitreal aflibercept in polypoidal choroidal vasculopathy: 12-month results of the PLANET study. Invest Ophthalmol Vis Sci. 2017;58(8):1199.
  26. ↑ Kokame GT, Lai JC, Wee R, et al. Prospective clinical trial of Intravitreal aflibercept treatment for polypoidal choroidal vasculopathy with hemorrhage or exudation (EPIC study): 6 month results. BMC Ophthalmol. 2016;16:127.
  27. ↑ Uyama M, Wada M, Nagai Y, et al. Polypoidal choroidal vasculopathy: natural history. Am J Ophthalmol. 2002;133(5):639-648.
  28. ↑ Lim TH, Laude A, Tan CS. Polypoidal choroidal vasculopathy: an angiographic discussion. Eye (Lond). 2010;24(3):483-490.
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