Pachychoroid spectrum disorders: a narrative review on intervortex venous anastomoses and associated choroidal vascular remodeling

Introduction

Pachychoroid spectrum disorders (PSD) comprise a group of retinochoroidal diseases, which are characterized by the thickening of the choroid, dilation of the vessels of the Haller layer, choroidal vascular hyperpermeability, and dysfunction of the choriocapillaris. PSD includes central serous chorioretinopathy (CSCR), pachychoroid neovasculopathy (PNV), polypoidal choroidal vasculopathy (PCV), peripapillary pachychoroid syndrome (PPS), and some other conditions. Although the exact prevalence of PSD is not known, the estimated prevalence of CSCR (0.014%) and PCV (0.31%) allows to consider PSD among four main maculopathies and retinopathies (1,2). Although CSCR has a broad spectrum of risk factors, among which male gender, smoking, hypertension, and hyperlipidemia are common with PCV (3,4). Risk factors for other conditions of the spectrum are not well-studied.

The mildest condition of PSD is pachychoroid pigment epitheliopathy, which may be considered either as a distinct entity or a sign of subclinical CSCR and is characterized by various retinal pigment epithelium (RPE) abnormalities associated with pachychoroid features in the absence of subretinal fluid accumulation (5). CSCR is a heterogeneous condition comprising acute and chronic forms. Acute CSCR is typically a self-limiting condition with subretinal fluid resolution within 3 months. Chronic CSCR, characterized by persistent subretinal fluid exceeding 6 months, is associated with significant RPE alterations and visual function deterioration (6). New multimodal CSCR classification includes simple and complex CSCR based on the area of RPE alteration (less or more than two optic disc areas) (7). The term PNV was introduced by Pang and Freund and refers to type one macular neovascularization developing in eyes with a pachychoroid phenotype. Key features include flat, irregular RPE elevation (“double-layer sign”) without evidence of age-related macular degeneration (8). PCV represents a subtype of type one macular neovascularization frequently associated with pachychoroid phenotype. It is characterized by aneurysmal-like vessel dilations on indocyanine green angiography (ICGA) or sharp-peaked RPE detachment with sub-RPE hyperreflective ring-like lesions, and a double-layer sign on optical coherence tomography (OCT) (9). A recently identified form of pachychoroid is PPS, which includes peripapillary pachyvessels and may present with sub- and intraretinal fluid sourced from the peripapillary area (10).

Characterization of PSD as a distinct group of diseases became possible with the introduction of OCT in enhanced depth imaging (EDI) mode, which allowed assessment of the thickness and the inner structure of the choroid. The last point was referred to the appearance so called pachyvessels. Understanding of PSD has improved considerably in recent years due to the growing number of studies focused on the choroidal venous outflow. Based on wide-field OCT and ICGA, the role of intervortex venous anastomoses (IVA) as a key element of vascular remodeling in pachychoroid was established. These vein-to-vein anastomoses, previously described with structural OCT as pachyvessels, cross the watershed zones and reflect insufficiency of venous outflow in one or several vortex vein systems. Although the pathophysiological importance of this new biomarker is understood, a standardized approach to its clinical evaluation and grading has not yet been proposed. Moreover, although a number of studies have analyzed individual aspects of choroidal changes with regard to the appearance of IVA, no studies have summarized all of these findings. Therefore, the aim of this review was to summarize data on the prevalence, pathophysiological role of IVA, their imaging, grading, and associated changes of the choroid in PSD based on ICGA and en face OCT. We present this article in accordance with the Narrative Review reporting checklist (available at https://aes.amegroups.com/article/view/10.21037/aes-25-31/rc).

Methods

In this paper, we reviewed relevant literature available in English reporting on the status of the IVA and associated choroidal vascular remodeling in healthy eyes as well as in any retinochoroidal disorders. We conducted a comprehensive electronic literature search using PubMed and Google Scholar databases. We included peer-reviewed articles reporting clinical and basic science research. The end date of peer-reviewed articles included in the review was March 2025. We included the following terms for the literature search in the context of the IVA and associated choroidal vascular remodeling “intervortex venous anastomoses”, “pachychoroid spectrum disorders”, “vortex veins”, “central serous chorioretinopathy”, “polypoidal choroidal vasculopathy”, and “peripapillary pachychoroid syndrome” (Table 1). The analysis included observational and non-interventional studies, encompassing randomized clinical trials, retrospective or prospective case-control studies, and cohort studies. Non-randomized interventional studies, case reports, conference abstracts, meeting proceedings, duplicate publications, unpublished materials, and editorial articles were excluded from the study. A manual search was also performed through the reference lists of selected articles. Two authors (D.S.M. and Y.A.K.) independently assessed study quality by evaluating the consistency between study titles, methods, and results. A third investigator (A.N.K.) adjudicated discrepancies when consensus could not be reached between the two primary investigators. Following the initial literature review, we analyzed imaging modalities of the vortex vein ampullae, their anatomical features in healthy eyes, eyes with PSD, and non-pachychoroid diseases, as well as their association with choroidal changes in PSD.

Discussion

Normal choroidal circulation

In contrast to microcirculation elsewhere, choroidal vessels are not embedded in tissue but are separated from the retina by the RPE and Bruch’s membrane. The choroid is supplied by short posterior ciliary arteries which penetrate the sclera within the peripapillary and macular region. Each artery is responsible for supplying a triangular area of the choroid with the base of the triangle facing the periphery of the eye fundus. These areas are not interconnected and may be independently involved in pathological conditions.

The choriocapillaris, the end pole of choroidal microcirculation, is organized in a lobular fashion where each unit has a central arteriole and peripheral venules which form venous collectors draining into large choroidal veins (11). Choroidal veins have no fractal pattern but rather form a net of multiple parallel large vessels passing the equator. The diameter of these veins increases when they fuse, but connections between them are rare until they form a venous collector referred to as the vortex vein. Between three to eight vortex veins leave the globe through the sclera and drain into the ophthalmic veins. In contrast to vessels in other parts of the body, choroidal veins do not follow the arterial network (12). In accordance with Murray’s law such system is not effective in terms of blood distribution; however, it is essential for maintaining adequate thermoregulation, high partial oxygen pressure, and intraocular pressure (13). Additionally, it allows asynchronous filling of choriocapillaris lobules (14).

The pattern of venous outflow is unique and independent for each quadrant of the eye fundus and all four quadrants of the eye fundus are separated by so-called choroidal watershed zones (15-17). The horizontal watershed zone passes through the optic nerve and divides the eye fundus into two superior and two inferior quadrants which collect the blood to two upper and lower systems of vortex veins. The vertical watershed zone passes between the optic disc and the center of the macula and separates temporal and nasal systems of vortex veins (18). Although venous outflow in each quadrant is independent, some connections between neighboring systems might be found in healthy eyes (19).

Global choroidal remodeling in pachychoroid

The choroid is a key element in the pathophysiology of a group of retinal diseases associated with choroidal thickening, PSD. From a clinical point of view, CSCR, PNV, and PCV are the most important. At the same time, CSCR seems to reflect the earliest stages of evolution of the pachychoroid and its uncomplicated course.

Until recently it remained undetermined if choroidal thickening depends mostly on extravascular fluid in cases of increased choroidal hyperpermeability or on vascular remodeling. With the progress of choroidal imaging, it was established that large choroidal vessels of the Haller’s layer are mostly responsible for the choroidal thickening (20-22). Currently, the most relevant explanation for this vascular remodeling is the presence of variable insufficiency of the choroidal venous outflow (23). One of the findings supporting this hypothesis is the appearance in eyes with PSD of IVA (17). By an analogy with retinal collaterals, IVA is considered to be not newly formed vessels but rather previously existing inactive anastomoses connecting systems of vortex veins and dilated in an attempt to allow a bypass for the blood from a dysfunctional system of vortex vein (24).

Choroidal imaging techniques

Today, two technologies allow en face imaging of choroidal vasculature and determine the presence of IVA: en face OCT and ICGA. Historically, ICGA was the first method to display the choroid; however, initially with a limited field of view. Moreover, this method is unable to assess choroidal thickness and has limited availability in routine practice. The introduction of spectral domain OCT and EDI mode enabled analysis of choroidal thickness and its inner structure as the vascularity index (25). Although the spatial organization of the choroidal vasculature cannot be evaluated based on cross-sectional OCT, its widespread distribution made available analysis of the choroid and the introduction of PSD. In fact, the data obtained with EDI OCT defined PSD as conditions associated with choroidal thickening due to dilation of large choroidal vessels also known as pachyvessels (26).

The current step in the progress in choroidal imaging is associated with swept-source OCT penetrating deeper to the choroid. Analysis of the choroid, IVA, and vortex veins has become available with advances in OCT scanning speed and image quality as well as with the expansion of the scanning area up to 24 mm. Moreover, in contrast to wide-field ICGA, this technique has better availability in respect of its noninvasive nature and time-saving (27). An optimal solution for the imaging of vortex veins and IVA is wide-field OCT, capturing vortex veins ampules. However, a limited number of OCT devices incorporate wide-field three-dimensional scanning. Therefore, in a typical situation, an examination can include a 12 to 18 mm scan centered in the center of the macula or a mosaic compounded from four or two smaller scans.

Irrespective of the scan size, another parameter for en face choroidal imaging with OCT is segmentation settings of the slab that should include the vessels of Haller’s layer. The thick slab robustly captures large choroidal vessels and is less dependent on their exact level within the choroid. However, the contrast of the image in such case decreases due to including the tissues lying above and below the vessels since the thickness of the choroid varies over the posterior pole. A thin slab, in contrast, highlights the luminal area. However, vessels passing at different levels may disappear from the slab and cannot be traced on the image. Several approaches for en face choroidal imaging were described depending on the OCT device used and actual status of the choroid. For example, a 100-µm slab can be placed 100 µm below the RPE with manual adjustment in every particular case (28). Alternatively, the slab may move from the Bruch’s membrane to the sclera until the best image of the large vessels is observed (29).

IVA

Evaluation of pachyvessels using ICGA and en face OCT confirm their role as IVA, since both methods allow tracking the pattern of these vessels crossing the watershed zones (Figure 1). Considering known characteristics of pachyvessels including hyperpermeability, compression of inner choroidal layers, colocalization with regions of RPE alterations and leakage, IVA take the role of one of the basic pathophysiological phenomena defining the clinical course of the disease. This is supported by the reduction of the diameter of dilated vessels after photodynamic therapy, which correlates with the regression of subretinal fluid (30). Regression of the disease activity is therefore related to normalization of choroidal venous outflow.

Figure 1 IVA in CSCR. (A) ICGA shows IVA (black arrowheads) crossing watershed zones (dashed lines). (B) Retro-mode scanning laser ophthalmoscopy shows accumulation of subretinal fluid (white arrowheads). CSCR, central serous chorioretinopathy; ICGA, indocyanine green angiography; IVA, intervortex venous anastomoses.

Appearance of IVA is described not only in PSD, but after circular scleral buckling (31), in radiation retinopathy (32), and in high myopia (33,34). Some studies describe IVA in different condition associated with venous overload choroidopathy not related to the PSD (13,35), including occlusions of vortex veins, spaceflight-associated neuro-ocular syndrome, carotid cavernous fistula (13,36), right ventricular failure, pulmonary hypertension, cardiomyopathy (13), superior vena cava syndrome (37), and idiopathic intracranial hypertension (38). However, the main problem remains the differentiation of IVA among other choroidal vessels.

Due to the absence of standardized definition for IVA in terms of quantitative and qualitative characteristics, there are some difficulties in assessment of this phenomenon based on OCT imaging. Fernández-Vigo et al. defined IVA as the connection between the supero-temporal and infero-temporal vortex vein systems, with a diameter ≥150 µm, which crosses the temporal raphe (28). Matsumoto et al. considered IVA to be presented when anastomosing vessels connect superior and inferior systems of vortex veins without narrowing toward the watershed zone (39). In general, the key characteristic of IVA is the crossing of the watershed zone by vessels of substantial diameter (40). Shiihara et al. consider a mean diameter of 153 µm to allow segregation of healthy and CSCR eyes (sensitivity and specificity of 82.9% and 68.3%, respectively) (22). Spaide et al. defined the presence of IVA as two or more vessels connecting neighboring quadrants with diameter equal or larger than the diameter of the retinal vessels at the edge of the optic disc (approximately 120 µm) (17). In cases where individual vessels are poorly distinguished, authors consider the absence of a visible watershed zone as a sign of the presence of multiple IVA (41). In general, in these studies, macular scans are used, and this partially explain the focus of the definitions on connections between temporal quadrants (28,30). Using ICGA, the definition of IVA losses topographical characteristics (i.e., localization in the macular area) and includes connection of any two vortex vein systems (42-44).

The lack of a unified approach to assessing IVA leads to subjective interpretation of data and limitations in cross-study comparisons. The potential for ambiguous results increases the risk of diagnostic and therapeutic errors, ultimately hindering the integration of this biomarker into routine clinical practice. To facilitate the adoption of IVA in both research and clinical settings, a standardized framework should be established.

Interestingly, existing studies use a macular scan, and nasal regions are therefore not adequately investigated. At the same time, we should bear in mind that the cross-section of watershed zones aligns with the optic disc not with the center of the macula. A scan centered on the optic disc would allow equal assessment of anastomotic connections at each sector of the peripapillary area. Another advantage of assessment of the peripapillary area for the presence of IVA is that the choroid is thinner in this region than in the macula, and this facilitates visualization of individual large vessels. In general, standardization is critical to ensure reproducibility and reduce bias in IVA evaluation.

IVA in healthy eyes

IVA is found in approximately 24–44% of the healthy population (19,44). In the majority of healthy individuals, large choroidal vessels have a symmetrical running pattern in relation to the horizontal watershed zone. However, in 38–50% of healthy eyes the normal geometry of the watershed zone may be altered by anomalous large choroidal vessels (29,45). In such case the dominant vortex vein appears most frequently in the superior-temporal quadrant (67%) or, less frequently, in the inferior-temporal of superior-nasal quadrants (17% in each case) (45). Despite these potentially abnormal features, the quantitative and qualitative characteristics of these large vessels are different compared to the true pachychoroid condition. Particularly, the distal portion of the vessels narrows closer to the watershed zone (20,46), their mean diameter being less than that of typical pachyvessels (22). Additionally, they do not contribute significantly to choroidal thickness (29), and the area of drained regions are more regularly distributed among separate vortex vein systems (42).

Although IVA may be found in healthy eyes, they do not meet criteria defining their functional activity. It seems that the simple appearance of IVA is not sufficient for pachychoroid status. The compression of the inner choroidal layer followed by the alteration of the RPE and leakage occurs only in substantial vertical asymmetry of IVA. High prevalence of dominance of the superior-temporal vortex veins and corresponding higher chance for asymmetry between upper and lower parts of the eye fundus may explain more frequent occurrence of the leakage in the upper segments of the macula (47,48).

IVA in PSD

Matsumoto et al. found anastomoses between superior and inferior vortex veins in 90% of PSD (44,49) which is substantially higher than in healthy eyes (50). In the pachychoroid spectrum, however, IVA have not only a higher prevalence but also characteristics of pachyvessels. Dilated IVA are associated with regions of hyperpermeability on ICGA, probably due to thinning of the vascular wall and its lower resistance to the increase venous pressure (46). IVA in eyes with active CSCR are more prevalent than in fellow healthy eyes or eyes of healthy individuals (17,28).

Most frequently IVA can be found in the regions of maximum choroidal thickness (42), in association with asymmetry (17), irregular diameter, cork-screw appearance, and abrupt termination (28) of large choroidal vessels, mostly in the superior-temporal quadrant. The correspondence between IVA, regions of thick choroid and choroidal hyperpermeability, and regions of RPE alteration leads us to consider them as a key biomarker in PSD (Figure 2).

Figure 2 Correspondence between IVA and choroidal hyperpermeability. (A) ICGA early phase shows multiple IVA (white arrowheads). (B) ICGA late phase shows choroidal hyperpermeability (black arrowheads). (C) Retro-mode scanning laser ophthalmoscopy shows neurosensory detachment (white arrows). (D) Fluorescein angiography shows the leakage point in the center of the macula (black arrow). ICGA, indocyanine green angiography; IVA, intervortex venous anastomoses.

Apart from simple identification, some attempts have been made to establish an association of topical distribution of IVA with the type of disease, its severity, and progression. In the majority of cases anastomoses were found in the macular region (28) with higher involvement of temporal vortex veins (17). This fact is explained by higher metabolic activity of this region, however, it is worth noting that these studies frequently use macular OCT scans, and a higher prevalence of anastomoses in the macular area is therefore to be expected (17). In cases of PNV (44) with peripapillary lesion, as well as in cases of PPS (17), IVA can be found around the optic disc (Figure 3). This fact as well as the passage of the watershed zones through the optic disc allows us to consider it as a virtual center around which IVA form.

Figure 3 IVA in PPS. (A) ICGA shows peripapillary IVA (arrowheads). (B) Late phase ICGA shows corresponding choroidal hyperpermeability (arrows). (C) Structural en face OCT projection shows peripapillary IVA and RPE disruption (asterisks). (D) Cross-sectional OCT scan shows subretinal and intraretinal fluid (black arrow). ICGA, indocyanine green angiography; IVA, intervortex venous anastomoses; OCT, optical coherence tomography; PPS, peripapillary pachychoroid syndrome; RPE, retinal pigment epithelium.

In accordance with some recent studies in eyes with CSCR, PNV, and PPS anastomoses mostly appear between the superior-nasal, superior-temporal, and inferior-temporal vortex veins systems. The inferior-nasal system less frequently demonstrates presence of IVA, with the exception of PPS, where IVA appear between all quadrants (17,28). In eyes with persistent CSCR inferior-nasal vortex vein may be the most frequently anastomosing compared to acute CSCR and demonstrates links with superior-temporal and inferior-temporal vortex veins (51). All of this suggests that the growing number of vortex veins communicated by IVA reflects a deterioration of the choroidal hemodynamic and the severity of the disease (Figure 4).

Figure 4 IVA in different forms of CSCR. (A) Healthy fellow eye of patient with unilateral CSCR. (B) Eye with active unilateral acute CSCR. (C) Eye of patient with bilateral chronic CSCR. CSCR, central serous chorioretinopathy; IVA, intervortex venous anastomoses.

Formation of IVA is associated with choroidal thickening; however, it is considered that over a long period their compensatory role may lead to the reduction of the thickness of the choroid and particularly the Haller layer (44,46), as well as vascular density (51) observed in eyes with chronic diseases. Notably, the area and the mean diameter of the vortex veins both reduce from CSCR to PNV to PCV, while the prevalence of IVA may increase (39,44).

Video-ICGA has demonstrated a retrograde pulsatile blood flow in vortex veins connected by IVA (52). A corresponding phenomenon of filling delay in choroidal veins was described using wide-field ICGA by Gemmy Cheung and coauthors in CSCR (53). This may indicate increased pressure in the venous pole of choroidal microcirculation ascending to the level of the choriocapillaris. The latter explains the delay in choriocapillaris filling which occurs in pachychoroid conditions. Interestingly, some higher prevalence of retrograde blood flow and delay filling may be observed in lower quadrants of the eye fundus (24,53). However, this may reflect the effects of gravitation force. The increased resistance to the venous outflow affecting choriocapillaris and possibly arterial level of the choroidal microcirculation may contribute to formation of polypoidal lesions in PCV (46). Some variability in localization of vortex veins may also play a role in defining the choroidal venous outflow. In this respect, Funatsu et al. suggested that in CSCR vortex veins of the superior-temporal quadrant formed at the greater distance from the optic disc than in healthy eyes (54).

All angiographic and morphological changes support the hemodynamic theory of PSD now called venous overload choroidopathy. This definition provides a substantial analogy with chronic venous insufficiency elsewhere in the body since all similar states share irregular venous dilation and engorgement of the tissues involved with opening of anastomotic connections. However, venous stasis is often associated with hemorrhages that were never seen in CSCR. In an animal model, however, obliteration of a vortex vein induces activation of IVA and some clinical signs of CSCR (31,32,55-57). However, these changes regress over time with restoration of normal choroidal anatomy. Therefore, despite significant controversies in etiology and pathogenesis of PSD, the role of IVA as an attempt to drain the regions of the choroid with excessive amount of fluid is quite clear. Exact correlations between IVA and disease severity require further investigation. However, they are obviously linked to the type and the course of the disease and may help in prediction of its outcome.

IVA in non-pachychoroidal conditions

Choroidal venous remodeling is not a unique feature of PSD and can be observed in axially elongated eyes. Several papers described IVA in highly myopic eyes which can be found around the optic disc (44–64%) or within the macular area (39–56%) (58-60). These IVA induce local choroidal thickening and are often observed in posterior staphyloma, tilted disc, and dome-shaped maculopathy (61-64). However, in contrast to PSD, these dilated vessels do not demonstrate hyperpermeability on ICGA (65). Nevertheless, the presence of dilated vessels has a specific clinical relevance, namely macular dilated choroidal vessels are associated with a more aggressive choroidal neovascularization phenotype and higher recurrence rate (66).

Some other features of PSD may be found in myopic eyes with serous maculopathy, namely thicker choroid (compared to myopic eyes without subretinal fluid) and dilated vessels with hyperpermeability (33,62). However, the accumulation of subretinal fluid is more likely observed in eyes with moderate myopia (−5.1 to −5.3 D) (61,62). It was suggested that not axial elongation but rather deformation of the posterior segment by a staphyloma affects choroidal microcirculation leading to so-called staphyloma-induced serous maculopathy where IVA were also documented (67).

Choroidal vascular remodeling associated with IVA

Choroidal thickness asymmetry

Although wide-field approach is important to analyze choroidal anatomy, the changes of the Haller’s layer in the central pole and macular area may reflect the general status of the choroidal venous outflow. Considering choroidal thickness as a function of venous congestion, asymmetry of choroidal thickness in the central area allows identification of the dilated vortex vein. This was confirmed by wide-field en face OCT Xephilio capturing 20–23 mm field of view, which identifies the dilated vortex vein and choroidal thickening along its route including the macular area (68). In most cases, a dominant vein can be found in both temporal quadrants with a similar frequency that corresponds to thicker choroid in temporal quadrants of the posterior pole (29). While automated assessment of choroidal thickness is still limitedly available, visual assessment of large choroidal veins may partially substitute for choroidal thickness mapping (Figure 5).

Figure 5 Choroidal thickening and asymmetry of the running pattern of choroidal vessels caused by IVA passing through macular region. (A) Structural en face OCT projection showing large vessels drained by lower temporal vortex vein. (B) Choroidal thickness map overlaying structural en face OCT projection shows correlation between choroidal thickening and the running pattern of choroidal vessels. IVA, intervortex venous anastomoses; OCT, optical coherence tomography.

Asymmetry of the running pattern of choroidal vessels

Since the Haller’s layer is the main contributor to choroidal thickness, the asymmetry of the running pattern of choroidal vessels reflects the distribution of choroidal thickness. In eyes with CSCR, asymmetry of the running pattern of choroidal vessels is one of the characteristic findings and reflects presence of the overloaded vortex veins which are dilated for the entire length from the distal end to the ampulla (Figure 6) (29,69). This asymmetry is defined by formation of the so-called dominant vein, which collects blood from the macular area and a significant fraction of the blood of the posterior pole in general. The dominant vortex vein has a larger diameter compared to other vortex veins and collects blood from a larger area of the eye fundus. It is mostly found in superior-temporal and inferior-temporal systems of vortex veins, while inferior-nasal system remains unchanged (29). However, some asymmetry of the running pattern of choroidal vessels may be found in 38–50% of healthy eyes, where superior-temporal system is also dominant (29,45).

Figure 6 Representative example showing asymmetry of the running pattern of choroidal vessels in CSCR. (A) Wide-field ICGA shows atypical drainage of macular area to upper nasal vortex vein (white arrowheads). (B) Magnified version of ICGA image in section (A). (C) Retro-mode scanning laser ophthalmoscopy shows correspondence between leak area (asterisk) and neurosensory detachment (black arrowheads) and IVA. (D) Structural en face OCT projection shows asymmetrical running pattern of large choroidal veins (dotted lines). CSCR, central serous chorioretinopathy; ICGA, indocyanine green angiography; IVA, intervortex venous anastomoses; OCT, optical coherence tomography.

Interestingly, earlier works which analyzed the running pattern of choroidal vessels in the macular area indirectly assessed the asymmetry in the dilation of vortex veins (70,71). The most frequent “temporal herringbone” pattern in healthy eyes corresponds to the presence of the watershed zone passing through the center of the macula horizontally. Since large vessels are normally absent in this area their impact on the retina in the middle of the macula is reduced compared to the superior segments (22). Fellow eyes of patients with unilateral CSCR also show greater diameter and asymmetry of the running pattern of choroidal vessels compared to eyes of healthy individuals (22).

In eyes with PSD higher variability in the size of zones drained by particular vortex veins compared to healthy eyes is observed (42). These eyes often demonstrate “reticular” pattern of the Haller’s layer. However, it is not fully understood if this pattern is of primarily or secondary nature (71).

A positive correlation is also found between choroidal vessel density in the central pole and the density of vortex vein ampullae (51). Eyes with PCV have a greater central vortex vein diameter, greater mean root area, and a higher number of vortex veins compared to healthy eyes. At the same time, the mean diameter of the thickest peripheral branch and central vortex vein diameter were greater than in eyes with age-related macular degeneration. In general, dilation of vortex veins is asymmetrical in PCV where the inferior temporal vortex vein is dominant (43). The asymmetry of the vortex veins correlates with shorter axial length and higher subfoveal choroidal thickness (72) and with a higher severity of CSCR (73). This suggests that the asymmetry of the Haller’s layer may be a compensatory mechanism for normalizing choroidal outflow in eyes with shorter axial length.

All of this suggest that analyzing asymmetry of the running pattern of choroidal vessels may be used as a surrogate for choroidal thickness mapping since the latter is rarely available.

Large vessel morphology

Dilation is a key characteristic of changes of the large choroidal vessels in PSD which were termed as pachyvessels after the introduction of enhanced depth OCT imaging. However, the quantitative and morphological assessment of pachyvessels was limited until progress in en face imaging.

Using en face OCT in eyes with CSCR it was shown that the area occupied by large vessels, as well as the length and diameter of these vessels are significantly higher than in healthy eyes. Compared to healthy fellow eyes, in eyes with active CSCR this difference was found only for vessel diameter, not for other characteristics (22). A positive correlation is also seen between choroidal vessel density and vortex vein ampullae density (30).

Assessment of large choroidal vessels revealed specific changes in their morphology, including “sausaging” (three consecutive regions of narrowing and dilation) and “bulbosities” (regions where the width of the vessel is twice that of the main vessel diameter) (74). Also corkscrew vessels were noted (28). Fusiform change was characterized by variation of the diameter by at least 50% from the narrowest to the thickest point (75) (Figure 7).

Figure 7 Structural en face OCT showing morphological abnormalizes of IVA in CSCR. White arrowheads indicate irregular diameter. CSCR, central serous chorioretinopathy; IVA, intervortex venous anastomoses; OCT, optical coherence tomography.

Determining the morphology of choroidal vessels can help in defining the pachychoroidal status and prognosis. According to the study by Jung et al., acute CSCR demonstrates lower choriocapillaris vessel density, likely due to less pronounced compression and alteration by underlying pachyvessels (76). Focal dilation of Haller’s layer vessels is predominantly observed in acute CSCR, while a more diffuse and homogeneous pattern is characteristic of chronic CSCR (77). Kogo et al. showed that with the increase of the difference in the vessel diameter index between superior and inferior temporal sectors, the chance for chronicity of CSCR also increases. Alternatively, cases with symmetrical choroidal vessel dilation, even if significant, typically show functionally active IVA and have a trend toward spontaneous regression of subretinal fluid (78). Continuous vascular remodeling in chronic CSCR, in turn, leads to subsequent choroidal thinning (76,79-81) and decline in choroidal vascularity index (25,82).

Arteriovenous choroidal anastomoses

Apart from the concept of IVA, the idea of arteriovenous anastomoses is also considered in PSD. The physiological role of these anastomoses includes regulation of blood supply in hypoxic conditions and thermoregulation. Arteriovenous anastomoses were described in the spinal cord, the external ear, and the episcleral (83,84). Their equivalent in the choroid includes arteriovenous fistula (85). Anatomically, the macular area is predisposed to the formation of arteriovenous fistula due to close proximity between arterial (short posterior ciliary arteries) and venous poles of the choroidal microcirculation (53). Interestingly, dural arteriovenous fistula appearing spinally, cranially, and near the cavernous sinus have similar risk factors as CSCR, including male gender and use of exogenous glucocorticosteroids (86,87).

Arteriovenous anastomosis/fistula allows passage of blood immediately from arteries to veins reducing blood supply to the capillary bed. This may lead to overload of venous pole, formation of large, dilated vessels and choroidal thickening similar to PSD. This venous overload may secondarily involve venous branches flowing into the vein connected to the arteriovenous anastomoses. Ascending venous dilation may involve collectors of choriocapillaris lobules that together with the compression by dilated veins able to lead to choriocapillaris dysfunction (84). IVA therefore may not be a primary element of choroidal hemodynamic disturbance but result from venous overload secondary to existing arteriovenous anastomoses. Moreover, topical and morphological characteristics of arteriovenous anastomosis/fistula may define the severity of the disease. Specifically, Brinks suggested that a single arteriovenous anastomosis and its spontaneous closure may correspond to acute CSCR, while multiple and persistent arteriovenous anastomoses result in chronic CSCR (84). The high efficacy of photodynamic therapy indirectly support the role of arteriovenous anastomoses since photosensitizer selectively accumulates in aberrant endothelium covering these structures (84,88). However, this concept requires further investigation since only one study has addressed this question.

Scleral anatomy as a cause of choroidal venous outflow insufficiency

Considering the path of choroidal venous outflow, which goes through the sclera, it is to be expected that scleral anatomy may define choroidal microcirculation (89). This suggestion is supported by the known correlation between choroidal thickness and axial length, which in turn correlates with scleral thickness (90). The thicker anterior sclera was indeed shown in CSCR (91,92) and PNV (93) including fellow eyes of unilateral CSCR patients (94). However this thickening mostly affects equatorial and anterior sclera rather than the posterior pole (95).

Scleral thickness is associated with PSD not only binomially but also is linked to the severity of the disease. Specifically, the sclera is thicker in complex CSCR with higher prevalence of choroidal fluid loculations and shallow ciliochoroidal detachments (96), and in higher choroidal vascularity index (97). At the same time no difference was found between affected and fellow CSCR eyes (98). In eyes with steroid-induced CSCR, the thickness of the sclera is lower than in idiopathic cases (99).

All of this suggests that thicker and rigid sclera may compromise choroidal venous outflow at the level of scleral channels of the vortex veins (100), through their elongation and narrowing, raising choroidal venous pressure followed by the global remodeling of the choroidal vasculature and accumulation of the fluid in suprachoroidal and subretinal space (92). The efficacy of partial sclerectomy in reducing CSCR symptoms supports this suggestion (101), as well as alleviating exudation in PPS along with reduction of scleral thickness under topical corticosteroids (102) (Figure 8).

Figure 8 Scleral thickness in complex and simple CSCR. (A) Cross-sectional OCT shows persistent neurosensory detachment in complex CSCR case. Dashed box delineates the region in section (C). (B) Anterior segment OCT demonstrates assessment of scleral thickness. (C) Anterior segment OCT demonstrates measurement of scleral thickness (white box), 433 μm. (D) Cross-sectional OCT shows subfoveal neurosensory detachment in simple CSCR case. Dashed box delineates the region in section (F). (E) Anterior segment OCT demonstrates assessment of scleral thickness. (F) Anterior segment OCT demonstrates measurement of scleral thickness (white box), 328 μm. CSCR, central serous chorioretinopathy; OCT, optical coherence tomography.

The role of the sclera is now under extensive investigation, yet it should not be excluded from speculative questions of PSD pathophysiology.

Limitations

Our narrative review represents the first study to summarize data on the prevalence IVA, their imaging characteristics, association with ophthalmic pathology, and prognostic significance. Understanding the mechanisms of venous drainage and vascular remodeling opens new avenues for developing strategies aimed at normalizing choroidal hemodynamics in PSD. However, our study has several limitations. Firstly, the literature review lacks longitudinal studies, making it difficult to analyze the causal relationship between IVA, choroidal remodeling, and disease progression. Secondly, many studies did not include quantitative or semi-quantitative assessment of IVA, which may lead to some level of subjectivity in the reported results. Thirdly, there is a lack of data on the role of peripheral anastomoses connecting the vortex vein systems, which appears logical given the contribution of central anastomoses to the clinical features of CSCR and other conditions of PSD. Finally, the studies were not standardized in terms of IVA assessment methodology, ethnic background, age, and gender distribution in the analyzed cohorts. However, despite these limitations, the consistency of findings across multiple studies supports the reliability of the conclusions obtained.

Conclusions

PSD today represents a number of conditions grouped together based on a simplistic sign, namely an increase of choroidal thickness. Although this criterion, together with an assessment of the choroidal vascularity index, makes it possible to diagnose diseases of the spectrum in routine practice using cross-sectional OCT, the pathogenetic mechanisms of PSD remain poorly understood. Today, with the introduction of wide-field ICGA and wide-field en face OCT, we understand the role of impaired venous outflow in PSD, where the activation of IVA plays a key role. This allows identification of the basic pathogenetic mechanism, venous overload choroidopathy, and its key morphological equivalent, which is responsible for the well-known signs of PSD: choroidal hyperpermeability, increased vascularity, the appearance of pachyvessels, and choroidal thickening. Thus, today we must shift the focus of clinical attention from these surrogate biomarkers to basic structural changes.

IVA is one of the few biomarkers reflecting the deep pathophysiological level of PSD. While subretinal exudation and RPE damage significantly impact the current functional status of the eye, they merely represent secondary effects of a deep underlying pathological process that begins long before clinical manifestation and persists thereafter. In contrast, choroidal remodeling may provide deeper insight into the overall course of the disease independent of the exudative status, thereby enabling better assessment of recurrence risk, fellow eye involvement, or the stability of remission. This highlights the need for further research into the clinical significance of choroidal hemodynamic remodeling in CSCR. Key priorities include elucidating the changes of IVA during conversion of healthy status to the pachychoroid phenotype, analyzing IVA morphological changes throughout the disease course, and evaluating post-treatment IVA dynamics. However, all of this requires standardization of IVA imaging and metrics. Focus on peripapillary region as the virtual center around which IVA appear may provide several potential advantages in this field and suggests that en face OCT can be a useful tool in analysis the morphology of the choroid in venous overload choroidopathy.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://aes.amegroups.com/article/view/10.21037/aes-25-31/rc

Peer Review File: Available at https://aes.amegroups.com/article/view/10.21037/aes-25-31/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aes.amegroups.com/article/view/10.21037/aes-25-31/coif). D.S.M. serves as an unpaid editorial board member of Annals of Eye Science from March 2025 to December 2026. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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