The Evolving Definition of the Pachychoroid Phenotype
The term pachychoroid (Greek: παχú, pachy, thick) describes a set of choroidal features first observed in patients with chronic central serous chorioretinopathy (CSC) and subsequently seen in a wider spectrum of disease including pachychoroid pigment epitheliopathy (PPE), pachychoroid neovasculopathy (PNV) and certain cases of polypoidal choroidal vasculopathy (PCV).1,2
Central serous chorioretinopathy (formerly central serous retinopathy) was originally described as a non-inflammatory neurosensory detachment at the posterior pole with fluorescein angiographic (FA) leakage at the level of the retinal pigment epithelium (RPE). The subsequent demonstration of co-localized mid-phase choroidal hyperpermeability together with pathological dilatation of choroidal vessels on indocyanine green angiography (ICGA) supported the hypothesis of a choroidal etiology.3-5
The development of optical coherence tomography (OCT) brought depth-resolution to the study of posterior segment disease. Spectral-domain technology and enhanced-depth imaging (EDI) showed that subfoveal choroidal thickness was typically increased in eyes with CSC and reduced in eyes with age-related choroidal atrophy and age-related macular degeneration (AMD).6-8
Combined cross-sectional and en face OCT localized the pathologically dilated choroidal vessels (“pachyvessels”) of CSC to Haller’s layer and revealed morphological features that distinguished them from normal Haller vessels.9 Additionally, thinning of the choriocapillaris and Sattler’s layer was noted, especially at disease foci where the loss of inner choroidal volume brought the pachyvessels into close proximity to the RPE-Bruch’s membrane complex.2,9,10
Patients with unilateral CSC exhibited these choroidal findings in the fellow eye, often with pigment epithelial hyperplastic changes, which were also co-localized with pachyvessels on OCT. These eyes were interpreted as having a forme fruste CSC and were described in the first publication on PPE.1
Although acute CSC is usually self-limited, chronic or recurrent CSC (spanning 6 months or more) may feature several complications, including RPE atrophy and neovascularization.11 However, the pattern of neovascularization in pachychoroid disease differs from that seen in neovascular AMD in a number of ways.2 Patients with PNV may be 10 to 15 years younger than patients with AMD at the time of onset of neovascularization, which generally occurs in the relative absence of drusen.
Furthermore, neovascularization in PNV usually occupies the sub-RPE compartment and manifests as a shallow irregular pigment epithelial detachment (PED).10 In the pachychoroid context, this type 1 neovascular tissue may be relatively quiescent and insidious in onset and its detection may be delayed because any subretinal fluid present may be attributed to CSC.10 Moreover, type 1 neovascularization in pachychoroid eyes may be difficult to detect by dye angiography; fluorescein hyperfluorescence may be ill-defined and small lesions which would otherwise be seen as plaques on ICGA may be rendered unresolvable by choroidal hyperpermeability.10,12
Polypoidal choroidal vasculopathy was first described by Yannuzzi and associates in terms of vascular lesions of uncertain etiology located deep to the RPE and visualized best on ICGA.13 Cross-sectional imaging with time-domain OCT showed that polypoidal lesions reside in the sub-RPE space where they arise from type 1 neovascular tissue, giving rise to peaked PEDs adjacent to shallow irregular PEDs, respectively.14
Although PCV shows a predilection for patients of Asian or African ancestry, it is often considered a variant of neovascular AMD. However, closer examination of Caucasian patients with polypoidal lesions has revealed that their choroids are thicker than those of patients with AMD, especially in areas adjacent to, or underlying, the neovascular lesions, and that this focal choroidal thickening is accounted for by the presence of pachyvessels rather than stromal expansion. Moreover, type 1 neovascularization with polypoidal lesions may be seen in patients in their 50s and 60s—an age group younger than is typical for neovascular AMD.
The resemblance of the clinical features of these patients to those with the pachychoroid phenotype of CSC has led to the hypothesis that PCV (or at least the variant seen in Caucasians) is more appropriately classified as a pachychoroid spectrum disorder than a variant of AMD.2,15 Whether this holds true for patients with Asian and African ancestry remains to be determined.
Genetically, preliminary studies examining single nucleotide polymorphism profiles in patients with CSC, neovascular AMD and PNV have shown similarities and differences in various risk allele frequencies. While similarities in polymorphism distribution between neovascular AMD and PNV suggest that certain risk alleles predispose to neovascularization in varied contexts (Freund et al, data under peer review), differences in distributions of other polymorphisms provide a genetic basis for a distinct pachychoroid phenotype to be recognized.16
Pang CE, Freund KB. Pachychoroid neovasculopathy. Retina. 2015;35(1):1-9.
Spaide RF, Hall L, Haas A, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina. 1996;16(3):203-213.
Guyer DR, Yannuzzi LA, Slakter JS, et al. Digital indocyanine green videoangiography of central serous chorioretinopathy. Arch Ophthalmol. 1994;112(8):1057-1062.
Pang CE, Shah VP, Sarraf D, Freund KB. Ultra-widefield imaging with autofluorescence and indocyanine green angiography in central serous chorioretinopathy. Am J Ophthalmol. 2014;158(2):362-371.
Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009;29(10):1469-1473.
Kuroda S, Ikuno Y, Yasuno Y, et al. Choroidal thickness in central serous chorioretinopathy. Retina. 2013;33(2):302-308.
Jonas JB, Forster TM, Steinmetz P, Schlichtenbrede FC, Harder BC. Choroidal thickness in age-related macular degeneration. Retina. 2014;34(6):1149-1155.
Dansingani KK, Balaratnasingam C, Naysan J, Freund KB. En face imaging of pachychoroid spectrum disorders with swept-source optical coherence tomography. Retina. 2016;36(3):499-516.
Dansingani KK, Balaratnasingam C, Klufas MA, Sarraf D, Freund KB. Optical coherence tomography angiography of shallow irregular pigment epithelial detachments in pachychoroid spectrum disease. Am J Ophthalmol. 2015;160(6):1243-1254.
Yannuzzi LA, Shakin JL, Fisher YL, Altomonte MA. Peripheral retinal detachments and retinal pigment epithelial atrophic tracts secondary to central serous pigment epitheliopathy. Ophthalmology. 1984;91(12):1554-1572.
Inoue M, Jung J, Balaratnasingam C, et al. A comparison between optical coherence tomography angiography and fluorescein angiography for the imaging of type 1 neovascularization (COFT-1). Invest Ophthalmol Vis Sci. In press.
Yannuzzi LA, Wong DW, Sforzolini BS, et al. Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration. Arch Ophthalmol. 1999;117(11):1503-1510.
Sato T, Kishi S, Watanabe G, Matsumoto H, Mukai R. Tomographic features of branching vascular networks in polypoidal choroidal vasculopathy. Retina. 2007;27(5):589-594.
Balaratnasingam C, Lee W, Koizumi H, Dansingani K, Inoue M, Freund KB. Polypoidal choroidal vasculopathy: a distinct disease or manifestation of many? Retina. 2016;36(1):1-8.
Miyake M, Ooto S, Yamashiro K, et al. Pachychoroid neovasculopathy and age-related macular degeneration. Sci Rep. 2015;5:16204.
About our author(s):
Kunal K. Dansingani, MA FRCOphth, Vitreous Retina Macula Consultants of New York; Truhlsen Eye Institute, University of Nebraska Medical Center; The LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital
K. Bailey Freund, MD, Vitreous Retina Macula Consultants of New York; The LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital; Department of Ophthalmology, New York University School of Medicine; Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University College of Physicians and Surgeons