To retina and beyond: What lies beneath

Image Credit: AdobeStock/Yulia

The retina plays the leading role when clinicians are viewing optical coherence tomography (OCT) scans. However, the choroid is often left out of the credits—a baffling oversight since this structure receives up to 85% of ophthalmic artery flow vs a measly 5% for the star of the show.¹ So why the disparity?

The choroid’s main responsibility is to supply nutrients and oxygen to the outer retina, where the highly metabolically active photoreceptors lie, and the retinal pigment epithelium (RPE). This is no small task. When compared with the macula, only the kidney receives more blood flow per unit weight.¹ With this in mind, this structure demands our attention.

Historically, we struggled to get a detailed choroidal view other than with our clinical examination, fundus photographs, and B-scan ultrasounds. Intravenous angiograms offered a better look, more so with the indocyanine green molecule due to its ability to stay within the choroidal vasculature longer, in addition to the deeper penetrating excitation wavelength. But things changed with spectral domain OCT (SD-OCT) and enhanced depth imaging (EDI). First described by Spaide et al in 2008, the EDI technique focused the OCT closer to the eye, which inverted the image but provided a deeper focus.² OCT manufacturers later gave us this scanning option but with a noninverted result.

Figure 1a. CSC, central serous chorioretinopathy; CVH, choroidal vascular hyperpermeability; ICGA, indocyanine green angiography; MNV, macular neovascular membrane; OCT, optical coherence tomography; RPE, retinal pigment epithelium.

Figure 1b.

These techniques resulted in the introduction of the pachychoroid (“pachy” means “thick”) spectrum (Figures 1a, 1b) in 2013, which unfortunately has still not made its way into the everyday practitioner’s vernacular. Though the pathogenesis is not completely understood, it appears dilated Haller vessels (called pachyvessels) pressure the overlying layers, which results in RPE dysfunction. Choriocapillaris filling delays occur in these areas when assessed with indocyanine green angiography (ICGA).³ Although lacking a standard size definition, spotting these pachyvessels often leads clinicians to the area of concern (ie, look above the pachyvessel in the EDI-OCT scan). Alternatively, you can detect the RPE changes and then look below for the pachyvessel.

Because what leads to Haller vessel enlargement and increased choroidal thickness remains unknown, several pathological theories exist. Pachychoroid eyes tend to exhibit increased choroidal vascular hyperpermeability (CVH) with ICGA, but not always.⁴ Other proposals include venous insufficiency choroidopathy, vortex vein ampulla obstruction, and venous overload choroidopathy.^5,6,7 Interestingly, and importantly, the choroidal expansion appears to occur much more often in hyperopic patients.

Figure 2a. Red-channel ultrawidefield image demonstrating nasal vortex vein anastomosis (yellow arrows). Figure 2b. Anastomosis occurring at the horizontal watershed zone (red arrow) as shown with indocyanine green angiography. Images courtesy of Jim Williamson, OD, FAAO, FORS.

A fascinating finding in current research is the detection of vortex vein anastomosis. Like retinal vasculature that remodels following a venous occlusion (ie, collaterals), the choroidal vasculature can also undergo changes. Normally the vortex veins respect a horizontal midline from the optic nerve to the macula and a vertical one through the optic nerve (ie, watershed zones). Spaide et al demonstrated intervortex venous anastomosis in pachychoroid-related disorders.⁵ While these authors employed ultrawidefield (UWF) ICGA to reveal this finding, the everyday practitioner can use the infrared picture captured with the EDI-OCT or an UWF image using the deeper penetrating red channel (Figure 2a). With pachychoroid, the traversing anastomosis favors the macular area (Figure 2b).

Figure 3. In a case of pachychoroid pigment epitheliopathy, a pachyvessel compresses the Sattler layer and choriocapillaris and causes focal retinal pigment epithelium and ellipsoid zone disruption, which clinically appears as pigment changes. Note the normal appearance outside the area. Image courtesy of Jim Williamson, OD, FAAO, FORS.

When originally described, 4 diseases comprised the pachychoroid spectrum. Warrow et al coined the term pachychoroid pigment epitheliopathy (PPE) to signal the pachychoroid spectrum’s first stage.⁸ In PPE, pigmentary changes occur in concert with a thickened choroid but without subretinal fluid (SRF) (Figure 3). Thus, PPE represents a forme fruste version of central serous chorioretinopathy (CSC).⁸ The significance of PPE is the potential for attribution to another disease, mostly age-related macular degeneration (AMD).

Figure 4a. Central serous chorioretinopathy at initial presentation vs 1 month later (B). Image courtesy of Jim Williamson, OD, FAAO, FORS.

Note the smooth undersurface in Figure 4b compared with the shaggy photoreceptor look at follow-up. Image courtesy of Jim Williamson, OD, FAAO, FORS.

Figure 4c. Fundus autofluorescence highlighting the hyperautofluorescence gravitational tract bordered with the yellow arrows. Image courtesy of Jim Williamson, OD, FAAO, FORS

Listed second in the spectrum is the archetypal CSC with its more obvious presentation of SRF. The slew of CSC risk factors includes steroid use, psychological stress, and sleep disturbances.⁹ CVH puts increased pressure on the RPE and restricts its ability to pump subretinal fluid. Pigment epithelial detachments (PEDs) occur, which may lead to pinpoint areas of leakage called RPE microrips.¹⁰ Signs of chronicity include shaggy photoreceptors, outer retinal atrophy, or gravitational tracts (Figure 4a, b, c).

Figure 5a. A 59-year-old patient previously diagnosed with unilateral age-related macular degeneration. The double-layer sign is present with a pachyvessel located directly below compressing the Sattler layer and choriocapillaris (yellow arrow). Drusen were not present. The patient’s diagnosis was reclassified to pachychoroid neovasculopathy. Figure 5b. A type 1 macular neovascularization membrane in another pachychoroid neovasculopathy patient with the double layer sign. Image courtesy of Jim Williamson, OD, FAAO, FORS.

Pachychoroid neovasculopathy (PNV) places third in the spectrum with the characteristic finding of the double layer sign (DLS). Normally, the RPE and Bruch’s membrane appear as a single line on OCT. In PNV, a type 1 macular neovascular membrane (MNV) separates the 2, creating the DLS (Figure 5a, b). Absent from this presentation are SRF, hemorrhages, and exudation. When it comes to detecting these characteristics, OCT angiography outperforms dye angiography.¹¹

Figure 6. Polypoidal choroidal vasculopathy/pachychoroid aneurysmal type 1 neovascularization. (6a) Spectral domain optical coherence tomography reveals the double layer sign and a large pigment epithelial detachment with significant subretinal fluid. (6b) Indocyanine green angiography showing hot spots (red arrows) that arise from the end of branching vascular networks, which is subtly noted here. Pooling of the spots may occur (yellow arrow). Images courtesy of Jim Williamson, OD, FAAO, FORS.

Polypoidal choroidal vasculopathy (PCV), or the alternatively suggested pachychoroid aneurysmal type 1 neovascularization (PAT1), rounds out the original diseases listed on the pachychoroid spectrum. The formation of aneurysms and/or polyps within the type 1 MNV—which appear as hot spots on ICGA—mark the presence of PCV/PAT1 (Figure 6). In 2020 the Asia-Pacific Ocular Imaging Society PCV Workgroup published a consensus nomenclature and non-ICGA diagnostic criteria for PCV/PAT1. Color fundus photographs highlight extensive subretinal hemorrhage and an orange nodule. Besides the obvious thick choroid and double layer sign, OCT features include a sharp-peaked PED, sub-RPE ringlike lesion, complex or multilobular PED, a fluid compartment, and en face OCT complex RPE elevation.¹²

Figure 7a. Conforming focal choroidal excavation. Image courtesy of Jim Williamson, OD, FAAO, FORS.

Figure 7b. Nonconforming focal choroidal excavation. Image courtesy of Jim Williamson, OD, FAAO, FORS.

Soon after the identification of these 4 conditions, 2 other pathologies joined the playing field with 2 more on the sidelines. Focal choroidal excavation (FCE), as its name suggests, denotes a localized structural defect that is not confined to just the pachychoroid spectrum. FCE is broken down into 2 types: conforming, where the RPE and retina follow the subsidence; and nonconforming, where the photoreceptors detach from the sinking RPE (Figure 7a, b).¹³ Peripapillary pachychoroid syndrome (PPS) takes the sixth spot with its thicker nasal macular choroid, placing its affects around the optic nerve. PPS characteristics include peripapillary intraretinal or SRF, serous PED, choroidal folds, short axial length, hyperopia, and a mostly bilateral presentation.¹⁴

Figure 8. Inferior temporal equatorial variegated hemorrhage in a patient with peripheral exudative hemorrhagic chorioretinopathy. Notice the conglomeration of drusen temporally (yellow arrow). Images courtesy of Jim Williamson, OD, FAAO, FORS.

The latest proposed entries include peripapillary pachychoroid neovasculopathy (PPN) and peripheral exudative hemorrhagic chorioretinopathy (PEHCR). PPN displays the DLS and CVH like PNV, but the type 1 neovascularization in PPN forms in the peripapillary region.¹⁵ PEHCR, however, differs from all the rest in that it occurs outside the posterior pole at the equator or beyond and with a temporal predeliction.¹⁶ Subretinal or sub-RPE hemorrhage with probable exudation accompany peripheral RPE changes and occasional drusen, making it the second most common pseudomelanoma (Figure 8).¹⁷ The discovery of polypoidal lesions within PEHCR and the novel finding of a peripherally thickened temporal choroid with pachyvessels led to its suggested entry into the pachychoroid spectrum.^16,18

Even with all the pathophysiological ideas and phenotypic descriptions, there still lacks a working pachychoroid definition. In 2021 Spaide scoured through 149 articles and found 18 unique designations and many more that were either undefined or contained ambiguities, though a more recent publication proposed the criteria listed in Figure 1b.^19,20 Of note is the article’s mention of pachydrusen. These are drusen larger than 125 μm that tend to occur in isolation around the optic nerve or in the posterior pole in patients whose mean subfoveal choroidal thickness (SFCT) is approximately 420 μm.²¹ Contrast this to soft drusen that favor the central macula, typically group with smaller drusen, display pigmentary changes, and have a mean SFCT nearly half that of pachydrusen.²¹ To compare, a typical choroidal thickness generally matches that of the overlying retina, although this is not entirely accurate since no exact value exists.

Regardless of all the inconsistencies with labeling and criteria for definition, the clinical importance of the pachychoroid spectrum is clear—acknowledge the entity and don’t misdiagnose it as another process. Going forward, activate the EDI setting when using SD-OCT to ensure the best choroidal view possible. Don’t attribute pigment changes in an at-risk demographic for AMD—look at the choroid, which is thinner in AMD patients. From now on when analyzing your OCT scans, let the choroid star alongside the retina and make EDI your new buzzword.

References:

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2. Spaide RF, Koizumi H, Pozonni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146(4):496-500. doi:10.1016/j.ajo.2008.05.032

3. Lejoyeux R, Benillouche J, Ong J, et al. Choriocapillaris: fundamentals and advancements. Prog Retin Eye Res. 2022;87:100997. doi:10.1016/j.preteyeres.2021.100997

4. Borooah S, Sim PY, Phatak S, et al. Pachychoroid spectrum disease. Acta Ophthalmol. 2021;99(6):e806-e822. doi:10.1111/aos.14683

5. Spaide RF, Ledesma-Gil G, Gemmy Cheung CM. Intervortex venous anastomosis in pachychoroid-related disorders. Retina. 2021;41(5):997-1004 doi:10.1097/IAE.0000000000003004

6. Kishi S, Matsumoto H. A new insight into pachychoroid disease: remodeling of choroidal vasculature. Graefes Arch Clin Exp Ophthalmol. 2022;260(11):3405-3417. doi:10.1007/s00417-022-05687-6

7. Spaide RF, Gemmy Cheung CM, Matsumoto H, et al. Venous overload choroidopathy: a hypothetical framework for central serous chorioretinopathy and allied disorders. Prog Retin Eye Res. 2022;86:100973. doi:10.1016/j.preteyeres.2021.100973

8. Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina. 2013;33(8):1659-1672. doi:10.1097/IAE.0b013e3182953df4

9. Liu B, Deng T, Zhang J. Risk factor for central serous chorioretinopathy: a systematic review and meta-analysis. Retina. 2016;36(1):9-19. doi:10.1097/IAE.0000000000000837

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12. Cheung CMG, Lai TYY, Teo K, et al. Polypoidal choroidal vasculopathy: consensus nomenclature and non-indocyanine green angiograph diagnostic criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup. Ophthalmology. 2021;128(3):443-452. doi:10.1016/j.ophtha.2020.08.006

13. Chung H, Byeon SH, Freund KB. Focal choroidal excavation and its association with pachychoroid spectrum disorders: a review of the literature and multimodal imaging findings. Retina. 2017;37(2):199-221. doi:10.1097/IAE.0000000000001345

14. Phasukkijwatana N, Freund KB, Dolz-Marco R, et al. Peripapillary pachychoroid syndrome. Retina. 2018;38(9):1652-1667. doi:10.1097/IAE.0000000000001907

15. Montero Hernández J, Remolí Sargues L, Monferrer Adsuara C, Castro Navarro V, Navarro Palop C, Cervera Taulet E. Peripapillary pachychoroid neovasculopathy: a novel entity. Eur J Ophthalmol. 2022;32(1):NP149-NP153. doi:10.1177/1120672120953071

16. Brown RB, Mohan S, Chhablani J. Pachychoroid disease spectrum disorders: an updated review. J Ophthalmic Vis Res. 2023;18(2)212-229. doi:10.18502/jovr.v18i2.13188

17. Shields CL, Salazar PF, Mashayekhi A, Shields JA. Peripheral exudative hemorrhagic chorioretinopathy simulating choroidal melanoma in 173 eyes. Ophthalmology. 2009;116(3):529-535. doi:10.1016/j.ophtha.2008.10.015

18. Shroff D, Sharma M, Chhablani J, Gupta P, Gupta C, Shroff C. Peripheral exudative hemorrhagic chorioretinopathy-a new addition to the spectrum of pachychoroid disease? Retina. 2021;41(7):1518-1525. doi:10.1097/IAE.0000000000003063

19. Spaide RF. The ambiguity of pachychoroid. Retina. 2021;41(2):231-237. doi:10.1097/IAE.0000000000003057

20. Yamashiro K, Yanagi Y, Koizumi H, et al. Relationship between pachychoroid and polypoidal choroidal vasculopathy. J Clin Med. 2022;11(15):4614. doi:10.3390/jcm11154614

21. Spaide RF. Disease expression in nonexudative age-related macular degeneration varies with choroidal thickness. Retina. 2018;38(4):708-716. doi:10.1097/IAE.0000000000001689