
==== Front
Jpn J Ophthalmol
Jpn J Ophthalmol
Japanese Journal of Ophthalmology
0021-5155
1613-2246
Springer Japan Tokyo

39150610
1101
10.1007/s10384-024-01101-2
Forefront Review
Central serous chorioretinopathy and the sclera: what we have learned so far
http://orcid.org/0000-0002-9610-4386
Koizumi Hideki hkoizumi@med.u-ryukyu.ac.jp

Imanaga Naoya
Terao Nobuhiro
https://ror.org/02z1n9q24 grid.267625.2 0000 0001 0685 5104 Department of Ophthalmology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa, 903-0215 Japan
16 8 2024
16 8 2024
2024
68 5 419428
14 4 2024
13 6 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Central serous chorioretinopathy (CSC) is a common disorder characterized by serous retinal detachment. Several studies using indocyanine green angiography (ICGA) have revealed that choroidal filling delay, choroidal vascular dilation, and choroidal vascular hyperpermeability are the characteristic findings of CSC. These ICGA findings confirm that choroidal circulatory disturbances are the primary factors in the pathogenesis of CSC. With advancements in optical coherence tomography (OCT), choroidal thickness has been found to be significantly greater in eyes with CSC than in normal eyes. Dilated large choroidal vessels reportedly account for the thickened choroid in eyes with CSC. Although many possible mechanisms and risk factors have been suggested, the pathophysiologic features of choroidal circulatory disturbances and choroidal thickening in eyes with CSC have not yet been fully elucidated. Recently, using anterior segment OCT, we proposed that the sclera may induce choroidal circulatory disturbances since CSC eyes have significantly thicker sclera than do normal eyes. This review summarizes updated information on the close relationship between CSC pathogenesis and the sclera.

Keywords

Central serous chorioretinopathy
Pachychoroid
Sclera
Uveal effusion syndrome
Vortex vein
http://dx.doi.org/10.13039/501100001691 Japan Society for the Promotion of Science JSPS KAKENHI 21K09746 Koizumi Hideki issue-copyright-statement© Japanese Ophthalmological Society 2024
==== Body
pmcIntroduction

Central serous chorioretinopathy (CSC) is a common disorder that predominantly affects middle-aged men and is characterized by serous retinal detachment [1]. Although retinal detachment resolves spontaneously in many cases, it often becomes chronic and develops secondary macular neovascularization, resulting in poor prognosis [2]. Indocyanine green angiography (ICGA) has dramatically improved our understanding of the pathogenesis of CSC and has revealed findings characteristic of CSC, such as choroidal filling delay, choroidal vascular dilation, and choroidal vascular hyperpermeability [3–6]. The consensus is that the choroid is the primary site of CSC pathogenesis. Recent advances in optical coherence tomography (OCT) have enabled us to obtain cross-sectional images of the choroid in daily practice, and choroidal thickening, dilation of large choroidal vessels, and thinning of the choriocapillaris are assumed to occur in eyes with CSC [7, 8]. These pathologic states of the choroid form the background for the development of serous retinal detachment. Other diseases with choroidal findings similar to those of CSC include pachychoroid pigment epitheliopathy, pachychoroid neovasculopathy, polypoidal choroidal vasculopathy, focal choroidal excavation, and peripapillary pachychoroid syndrome, which are referred to as pachychoroid spectrum diseases and suggest a common underlying pathogenesis [9]. Known risk factors for CSC include psychologic stress, type A personality, steroids (exogenous and endogenous), pregnancy, and sleep apnea, all of which have been implicated in the sympathetic nervous system [1]. Other factors such as hypertension, smoking, alcohol consumption, Helicobacter pylori infection, and several genetic mutations (TNFRSF10A and GATA5) have been reported [1]. Recent developments in ocular imaging have deepened our understanding of CSC pathogenesis. Saito and colleagues [10] used laser speckle flowgraphy to reveal choroidal hyperperfusion and choroidal blood flow imbalance in eyes with CSC. They reported that these findings could be explained by increased sympathetic activity, which causes choroidal hyperperfusion owing to increased ocular perfusion pressure caused by increased cardiac output due to systemic β-activation and choroidal blood flow imbalance due to increased vascular resistance caused by the constriction of choroidal small arterioles due to local α-activation in the eye. Recently, en face OCT has been reported to show characteristic findings in eyes with CSC, such as asymmetrically dilated vortex veins [11] and choroidal vascular anastomoses [12]. Widefield ICGA shows dilated vortex veins extending into the ampulla in CSC eyes, indicating that CSC involves the macular area and the entire fundus of the eye [13]. Furthermore, widefield OCT shows continuous choroidal thickening from the vortex vein ampulla to the macula, suggesting that some mechanisms cause the vortex veins to fail to drain out of the eye in eyes with CSC [14, 15]. Treatments for CSC include traditional laser photocoagulation, micropulse laser therapy, photodynamic therapy (PDT) with verteporfin, and oral administration of mineralocorticoid antagonists [1]. Recent randomized controlled trials have recommended half-dose or half-fluence PDT with laser photocoagulation limited to situations in which PDT is not available, early improvement is desired for occupational or other reasons, and the site of leakage on fluorescein angiography is outside the central fovea [1]. PDT is a valuable treatment that focuses more on the pathology because it successfully diminishes choroidal vascular hyperpermeability in the irradiated area [16], thins the pathologically thickened choroid [17], and narrows dilated large choroidal vessels [18]. Surprisingly, a decrease in choroidal thickness and choroidal vascular caliber was observed in the PDT-irradiated area and more extensively beyond the retinal vascular arcade [19, 20].

Scleral thickness in CSC

The findings mentioned above suggest an obstruction to the outflow of the vortex vein to the outside of an eye with CSC, resulting in choroidal venous congestion. Because the vortex vein in the quadrants of the choroid obliquely penetrates the sclera at the equator with a length of approximately 4 mm and drains out of the eye (Fig. 1), it is reasonable to assume that there are problems with the sclera, such as its penetration pathway. We have previously reported that the axial length of the eye is shorter and more hyperopic in CSC eyes than in normal eyes and that this tendency is more pronounced in bilateral CSC than in unilateral CSC, suggesting that ocular anatomic factors influence the pathogenesis of CSC [21]. Ideally, obtaining a cross-sectional image of the sclera and evaluating it in comparison to that of a normal eye could significantly contribute to our understanding of CSC pathogenesis. However, it is not easy to obtain cross-sectional images of the sclera with current OCT systems for the posterior region of the eye, and research has been limited to highly myopic eyes, where entire cross-sectional images of the sclera can be obtained [22]. Therefore, we attempted to acquire scleral cross-sectional images using an anterior rather than a posterior approach. However, ultrasound biomicroscopy is not suitable for accurate evaluation of scleral cross-sectional images because it is complicated: only a narrow area of the image can be obtained, the resolution is low, and above all, the sclera cannot be separated from the surrounding conjunctiva or connective tissue [23]. Therefore, we evaluated the sclera using swept-source anterior segment OCT (CASIA 2; Tomey). We found that when patients were asked to perform eye movements to obtain images under the 4 recti muscles, the recti muscles were rendered in low intensity and the sclera in high intensity by OCT, making it possible to obtain cross-sectional images of the sclera without influence from the surrounding tissue and to measure its thickness quantitatively [24] (Fig. 2). Accordingly, we compared the scleral thicknesses of 47 eyes of 40 patients with CSC with those of 53 eyes of 47 normal controls matched for age and sex, 6 mm posterior to the scleral spur. The mean scleral thickness was significantly greater in the CSC eyes than in the normal eyes in all 4 directions: the superior (429.4 μm vs. 395.2 μm; P = .005), temporal (447.7 μm vs. 396.5 μm; P < .001), inferior (455.7 μm vs. 437.8 μm; P = .022), and nasal (454.9 μm vs. 416.6 μm; P = .001) points, despite the absence of differences in spherical equivalent and axial length between the groups [24] (Fig. 3). Subsequent reports have also shown that the anterior and posterior sclera were thicker in CSC eyes than in normal eyes on anterior segment OCT [25–27] and ultrasound B-mode [28], and a consensus has been reached regarding scleral thickening in CSC eyes [29, 30]. We further investigated the separation of the luminal and stromal portions of the choroid using a binarization technique and reported that scleral thickness positively correlates with the choroidal luminal/stromal ratio in eyes with CSC [31]. In other words, thicker sclera in eyes with CSC indicates that the choroid changes to a more pachychoroid-like structure.

Fig. 1 Schematic representation of the choroidal circulation. The vortex vein obliquely penetrates the sclera at the equator with a length of approximately 4 mm and drains out of the eye

Fig. 2 Anterior segment optical coherence tomography images used to measure scleral thickness acquired by gazing in 4 directions (superior, temporal, inferior, and nasal). a Scleral spur distinguished by the difference in reflectivity between the sclera and ciliary body. The episcleral vessel and rectus muscle were visualized by a low reflective line and a low reflective band, respectively. b Anterior and posterior scleral boundaries were determined. c Scleral thickness was measured vertically 6 mm posterior to the scleral spur. A line was drawn perpendicularly to a line parallel to the inner wall of the sclera, and the thickness of the sclera was measured manually.

Reprinted from Imanaga and colleagues [24] with permission from Elsevier

Fig. 3 a Horizontal B-scan optical coherence tomography (OCT) image of a 45-year-old man with central serous chorioretinopathy showing serous retinal detachment with a subfoveal choroidal thickness of 469 μm. Significant dilation of the choroidal vessels under the fovea was observed. b Cross-sectional image of the temporal sclera of the same man shown in a, obtained using anterior segment OCT. The scleral thickness was 442 μm. The asterisk represents the lateral rectus muscle. c Horizontal B-scan swept-source OCT image of a 46-year-old man showing no significant findings with a subfoveal choroidal thickness of 320 μm. d Cross-sectional image of the temporal sclera of the same man shown in c, obtained using anterior segment OCT. The scleral thickness was 276 μm. The asterisk represents the lateral rectus muscle.

Reprinted from Imanaga and colleagues [24] with permission from Elsevier

Scleral thickness and suprachoroidal fluid accumulation in CSC

We further investigated the relationship between scleral thickness and suprachoroidal fluid accumulation, i.e., loculation of fluid (LOF) [32] and peripheral ciliochoroidal effusion (CE) [33], in eyes with CSC. LOF was first proposed by Spaide and Ryan in 2015 [34]. They found a high frequency of hyporeflective areas on OCT that were not choroidal vessels, which they described as fluid retention in the outer choroidal layer or suprachoroidal space. According to the same report, LOF was present in 64.8% of CSC eyes [34]; in our study, LOF was observed in 98 of 158 CSC eyes (62.0%) [32] (Figs. 4 and 5). The presence of LOF was significantly and independently associated with a thick sclera and a thick choroid. Furthermore, we observed subclinical CE using anterior segment OCT and found that the presence of CE in 1 or more of the 4 directions was significantly more common in CSC eyes (32 of 164 eyes, 19.5%) than in normal control eyes (1 of 50 eyes, 2.0%) [33] (Fig. 6). Furthermore, multivariable analysis showed that a thick sclera was the sole factor significantly associated with CE. In other words, scleral thickening may cause fluid retention in the choroid through vortex vein congestion and another pathway of decreased transscleral permeability from the intraocular to the extraocular space. In fact, the presence of CE was not associated with CVH areas, which supports this theory [33]. Subretinal fluid is usually seen as a characteristic feature of CSC in our daily practice; however, in the opposite direction, thick sclera may induce subclinical suprachoroidal fluid, such as LOF and CE (Fig. 7).

Fig. 4 Right eye of a 51-year-old man with central serous chorioretinopathy. Horizontal B-scan with optical coherence tomography showing serous retinal detachment and pigment epithelial detachment. The subfoveal choroidal thickness was 475 μm. Dilation of the choroidal vessels under the fovea was observed. Loculation of fluid was present in the outer choroid (white arrowheads).

Reprinted from Imanaga and colleagues [32]

Fig. 5 En face images of the case shown in Fig. 4. Volume scan data captured a 12 × 9-mm area centered at the midpoint between the foveal center and optic disc. The en face image was flattened at the level of the Bruch membrane. These en face images show the outside of the Bruch membrane from 273 to 507 μm at intervals of 26 μm. Loculation of fluid exists under the outer choroid and was confirmed to be free from connections to the horizontal and vertical choroidal vessels by use of en face images (white arrowheads).

Reprinted from Imanaga and colleagues [32]

Fig. 6 Representative case of the right eye of a 42-year-old man with central serous chorioretinopathy with ciliochoroidal effusion. a Color fundus photography showed subretinal fluid and a descending tract with an alteration of the retinal pigment epithelium in the macular area. b Optical coherence tomography (OCT) along the white dotted line in a revealed subretinal fluid and pachychoroid with markedly dilated choroidal vessels. The subfoveal choroidal thickness was 537 μm. c Fluorescein angiography demonstrated several leakages in the macular area. The descending tracts corresponded to the hyperfluorescent areas with window defects. d Indocyanine green angiography revealed multifocal areas of choroidal vascular hyperpermeability (red arrows). Anterior segment OCT demonstrated cross-sectional images of the anterior sclera in 4 directions (e superior, f temporal, g inferior, and h nasal). Ciliochoroidal effusion (arrowheads) was evident as a clearly hyporeflective area between the sclera and the ciliary body or the choroid at the superior, temporal, and inferior points. The scleral thicknesses at the superior, temporal, inferior, and nasal points were 472 μm, 534 μm, 539 μm, and 493 μm, respectively.

Reprinted from Terao and colleagues [33] with permission from Wolters Kluwer Health

Fig. 7 Schematic representation of fluid movement in central serous chorioretinopathy (CSC). Subretinal fluid is a characteristic feature of CSC; however, in the opposite direction, a thick sclera induces subclinical suprachoroidal fluid, such as loculation of fluid (LOF) and ciliochoroidal effusion (CE)

CSC and uveal effusion syndrome (UES)

As mentioned previously, a short axial length, hyperopia, scleral thickening, and fluid accumulation in the suprachoroidal space suggest some pathologic overlap between CSC and UES [35]. CSC is rare in highly myopic eyes [36], and some overlap exists in the clinical findings of both diseases, including choroidal circulatory disturbance [35], retinal detachment [35], and leopard spot pattern [37]. In addition, UES is not always associated with typical nanophthalmos [35]. More recently, reports of CSC complicated by typical UES findings have been published [38–40]. Additionally, sclerotomy, the standard treatment for UES, has shown an excellent response to severe CSC [41, 42], suggesting an overlap between the pathogenesis of CSC and UES. Recently, the CSC International Group proposed a classification system using multimodal imaging based on the range of retinal pigment epithelium (RPE) atrophy areas for objective evaluation of CSC [43]. We compared the scleral thicknesses of the 2 groups, namely, simple CSC (RPE atrophy ≤ 2 disc areas) and complex CSC (RPE atrophy > 2 disc areas), and found that the mean scleral thickness was greater in all 4 directions in complex CSC than in simple CSC (448.4 μm vs. 403.6 μm, 466.8 μm vs. 422.0 μm, 482.1 μm vs. 439.7 μm, 479.2 μm vs. 423.6 μm, in the superior, temporal, inferior, and nasal directions, respectively; all P < .001) [44] (Figs. 8 and 9). In other words, CSC and UES form the same group of “pachysclera spectrum diseases,” and complex CSC may be in a continuous position between simple CSC and UES.

Fig. 8 Representative case of the left eye of a 42-year-old woman with simple central serous chorioretinopathy. a Color fundus photography revealed serous retinal detachment in the macula. b Fundus autofluorescence photography demonstrated a tiny alteration of the retinal pigment epithelium. c Horizontal B-scan optical coherence tomography (OCT) showed high serous retinal detachment. The subfoveal choroidal thickness was 300 μm. Cross-sectional images of the sclera in 4 directions (d superior, e temporal, f inferior, and g nasal) were obtained using anterior segment OCT. The scleral thicknesses at the superior, temporal, inferior, and nasal points were 290, 290, 322, and 313 μm, respectively.

Reprinted from Imanaga and colleagues [44]

Fig. 9 Representative case of the right eye of a 51-year-old man with complex central serous chorioretinopathy. a Color fundus photography revealed serous retinal detachment in the macula and retinal pigment epithelium (RPE) alteration. b Fundus autofluorescence photography demonstrated a total RPE atrophy area larger than 2 disc areas. c Horizontal B-scan optical coherence tomography (OCT) image showed serous retinal detachment and ellipsoid zone attenuation. The subfoveal choroidal thickness was 502 μm. The loculation of fluid was visualized as a hyporeflective area that was not contiguous with the vessels beneath the dilated choroidal vessels (yellow arrows). Cross-sectional images of the sclera in 4 directions (d superior, e temporal, f inferior, and g nasal) were obtained by use of anterior segment OCT. The scleral thicknesses at the superior, temporal, inferior, and nasal points were 544, 554, 581, and 572 μm, respectively. Ciliochoroidal effusion was confirmed by a hyporeflective area between the sclera and the ciliary body on anterior segment OCT images in all 4 directions (white arrows).

Reprinted from Imanaga and colleagues [44]

Scleral thickness in steroid-induced CSC

Steroids are one of the most important risk factors for the development of CSC [1]. Therefore, what is the involvement of the sclera in steroid-induced CSC? To answer this question, we compared scleral thickness in 96 eyes with idiopathic CSC and 14 eyes with steroid-induced CSC [45]. The results showed that the mean scleral thickness was thinner in steroid-induced CSC than in idiopathic CSC at the superior (346.6 μm vs. 423.4 μm; P < .001), temporal (399.4 μm vs. 440.1 μm; P = .020), inferior (395.3 mm v 450.1 mm; P = .001), and nasal (391.9 μm vs. 436.6 μm; P = .002) points. This result suggests that the sclera is less involved in the pathogenesis of steroid-induced CSC than of idiopathic CSC.

Scleral thickness and vortex vein asymmetry in CSC

Asymmetrical dilation of vortex veins is a characteristic feature of the choroidal vasculature in eyes with CSC [11]. Is scleral thickening associated with vortex vein asymmetry? We examined en face OCT findings for factors associated with vortex vein asymmetry and found no association with scleral thickening, although a short axial length was significantly associated [46]. Interestingly, choroidal vascular asymmetry was associated with ocular anatomic factors. The asymmetric vortex veins may result in an unbalanced distribution of choroidal venous blood flow, causing congestion of certain vortex veins that may contribute to choroidal thickening and increased choroidal vascular hyperpermeability in their dominant regions [47]. Although a certain percentage of asymmetry is observed even in normal eyes [11, 48], this percentage does not increase with age, suggesting that it may be congenitally or genetically defined to some extent.

Scleral thickness in unilateral CSC

Is scleral thickening sufficient for CSC development? CSC is often triggered by stress or exposure to steroids. To answer this question, we compared the scleral thickness of the affected and unaffected eyes of patients with unilateral CSC [49]. No differences were found in spherical equivalent, axial length, anterior chamber depth, or frequency of CE, nor in scleral thickness between the affected and unaffected fellow eyes in any of the 4 directions. The only difference between the 2 groups was in subfoveal choroidal thickness, which was significantly greater in the affected eyes than in the unaffected fellow eyes. Therefore, choroidal thickening is involved in the direct pathogenesis of CSC, and scleral thickening is an underlying factor in the development of CSC.

Proposed pathophysiology of CSC

The concept of the “two-hit theory” was recently proposed to describe the pathophysiology of CSC [50]. First, anatomic factors, such as scleral thickening [24], short axial length [21], and vortex vein asymmetry [11], which may be congenital factors, seemingly cause vortex vein congestion and decreased transscleral outflow. Next, some triggers, such as stress and steroids, may further induce more vortex vein congestion, extravascular leakage, and fluid accumulation in the choroid, resulting in subretinal and suprachoroidal fluid accumulation, although where and how these triggers work remain unclear. The proposed pathophysiology of CSC is depicted in Fig. 10.

Fig. 10 Proposed pathophysiology of central serous chorioretinopathy. First, anatomic factors, such as scleral thickening, short axial length, and vortex vein asymmetry, which may be congenital factors, seemingly cause vortex vein congestion and decreased transscleral outflow. Next, triggers, such as stress and steroids, may further induce more vortex vein congestion, extravascular leakage, and fluid accumulation in the choroid, which finally results in subretinal and suprachoroidal fluid accumulation, such as loculation of fluid (LOF) and ciliochoroidal effusion (CE)

Future perspective

As discussed above, evidence for scleral involvement in CSC is increasing. Although evidence has been established for PDT as an effective treatment, cases of recurrence refractory to long-term treatment still exist [1]. Furthermore, the current shortage of verteporfin is a serious challenge worldwide [51], and new alternative treatments should be explored. Specifically, we would like to see the development of minimally invasive treatments targeting the sclera, especially in refractory CSC. However, our current scleral evaluation methods have limitations. First, scleral thickness measurements were performed manually. Second, we still cannot capture the site of vortex vein penetration through the sclera. Finally, only quantitative evaluations of the sclera have been conducted; qualitative evaluations will present challenges in the future. Nevertheless, apart from CSC, the pachychoroid is also suspected to be responsible for some other disorders, such as approximately 20% of dry age-related macular degeneration [52] and 50% of neovascular age-related macular degeneration [53] in the Japanese population. Detailed evaluation of the sclera in these diseases may lead to new pathophysiology, more optimal treatment, and prevention of vision-threatening conditions.

Acknowledgements

This study was supported by JSPS Kakenhi (grant number 21K09746). The authors thank Editage (www.editage.com) for English language editing.

Declarations

Conflict of interest

H. Koizumi, None; N. Imanaga, None; N. Terao, None.

Organizer: Akitaka Tsujikawa, MD

Corresponding Author: Hideki Koizumi

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Feenstra HMA, van Dijk EHC, Cheung CMG, Ohno-Matsui K, Lai TYY, Koizumi H et al. Central serous chorioretinopathy: an evidence-based treatment guideline. Prog Retin Eye Res. 2024:101236.
2. Shiragami C Takasago Y Osaka R Kobayashi M Ono A Yamashita A Clinical features of central serous chorioretinopathy with type 1 choroidal neovascularization Am J Ophthalmol 2018 193 80 6 10.1016/j.ajo.2018.06.009 29940168
Shiragami C, Takasago Y, Osaka R, Kobayashi M, Ono A, Yamashita A, et al. Clinical features of central serous chorioretinopathy with type 1 choroidal neovascularization. Am J Ophthalmol. 2018;193:80–6.29940168
3. Hayashi K Hasegawa Y Tokoro T Indocyanine green angiography of central serous chorioretinopathy Int Ophthalmol 1986 9 37 41 10.1007/BF00225936 3721709
Hayashi K, Hasegawa Y, Tokoro T. Indocyanine green angiography of central serous chorioretinopathy. Int Ophthalmol. 1986;9:37–41.3721709
4. Piccolino FC Borgia L Central serous chorioretinopathy and indocyanine green angiography Retina 1994 14 231 42 10.1097/00006982-199414030-00008 7973118
Piccolino FC, Borgia L. Central serous chorioretinopathy and indocyanine green angiography. Retina. 1994;14:231–42.7973118
5. Spaide RF Hall L Haas A Campeas L Yannuzzi LA Fisher YL Indocyanine green videoangiography of older patients with central serous chorioretinopathy Retina 1996 16 203 13 10.1097/00006982-199616030-00004 8789858
Spaide RF, Hall L, Haas A, Campeas L, Yannuzzi LA, Fisher YL, et al. Indocyanine green videoangiography of older patients with central serous chorioretinopathy. Retina. 1996;16:203–13.8789858
6. Iida T Kishi S Hagimura N Shimizu K Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy Retina 1999 19 508 12 10.1097/00006982-199911000-00005 10606450
Iida T, Kishi S, Hagimura N, Shimizu K. Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy. Retina. 1999;19:508–12.10606450
7. Imamura Y Fujiwara T Margolis R Spaide RF Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy Retina 2009 29 1469 73 10.1097/IAE.0b013e3181be0a83 19898183
Imamura Y, Fujiwara T, Margolis R, Spaide RF. Enhanced depth imaging optical coherence tomography of the choroid in central serous chorioretinopathy. Retina. 2009;29:1469–73.19898183
8. Yang L Jonas JB Wei W Choroidal vessel diameter in central serous chorioretinopathy Acta Ophthalmol 2013 91 e358 62 10.1111/aos.12059 23647989
Yang L, Jonas JB, Wei W. Choroidal vessel diameter in central serous chorioretinopathy. Acta Ophthalmol. 2013;91:e358–62.23647989
9. Cheung CMG Lee WK Koizumi H Dansingani K Lai TYY Freund KB Pachychoroid disease Eye (Lond) 2019 33 14 33 10.1038/s41433-018-0158-4 29995841
Cheung CMG, Lee WK, Koizumi H, Dansingani K, Lai TYY, Freund KB. Pachychoroid disease. Eye (Lond). 2019;33:14–33.29995841
10. Saito M Saito W Hirooka K Hashimoto Y Mori S Noda K Pulse waveform changes in macular choroidal hemodynamics with regression of acute central serous chorioretinopathy Invest Ophthalmol Vis Sci 2015 56 6515 22 10.1167/iovs.15-17246 26447987
Saito M, Saito W, Hirooka K, Hashimoto Y, Mori S, Noda K, et al. Pulse waveform changes in macular choroidal hemodynamics with regression of acute central serous chorioretinopathy. Invest Ophthalmol Vis Sci. 2015;56:6515–22.26447987
11. Hiroe T Kishi S Dilatation of asymmetric vortex vein in central serous chorioretinopathy Ophthalmol Retina 2018 2 152 61 10.1016/j.oret.2017.05.013 31047342
Hiroe T, Kishi S. Dilatation of asymmetric vortex vein in central serous chorioretinopathy. Ophthalmol Retina. 2018;2:152–61.31047342
12. Matsumoto H Hoshino J Mukai R Nakamura K Kikuchi Y Kishi S Vortex vein anastomosis at the watershed in pachychoroid spectrum diseases Ophthalmol Retina 2020 4 938 45 10.1016/j.oret.2020.03.024 32651158
Matsumoto H, Hoshino J, Mukai R, Nakamura K, Kikuchi Y, Kishi S, et al. Vortex vein anastomosis at the watershed in pachychoroid spectrum diseases. Ophthalmol Retina. 2020;4:938–45.32651158
13. 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 158 362 e712 10.1016/j.ajo.2014.04.021 24794091
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;158:362–e712.24794091
14. Ishikura M Muraoka Y Nishigori N Takahashi A Miyake M Ueda-Arakawa N Widefield choroidal thickness of eyes with central serous chorioretinopathy examined by swept-source OCT Ophthalmol Retina 2022 6 949 56 10.1016/j.oret.2022.04.011 35436598
Ishikura M, Muraoka Y, Nishigori N, Takahashi A, Miyake M, Ueda-Arakawa N, et al. Widefield choroidal thickness of eyes with central serous chorioretinopathy examined by swept-source OCT. Ophthalmol Retina. 2022;6:949–56.35436598
15. Funatsu R Sonoda S Terasaki H Shiihara H Mihara N Horie J Choroidal morphologic features in central serous chorioretinopathy using ultra-widefield optical coherence tomography Graefes Arch Clin Exp Ophthalmol 2023 261 971 9 10.1007/s00417-022-05905-1 36401650
Funatsu R, Sonoda S, Terasaki H, Shiihara H, Mihara N, Horie J, et al. Choroidal morphologic features in central serous chorioretinopathy using ultra-widefield optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2023;261:971–9.36401650
16. Chan WM Lai TY Lai RY Tang EW Liu DT Lam DS Safety enhanced photodynamic therapy for chronic central serous chorioretinopathy: one-year results of a prospective study Retina 2008 28 85 93 10.1097/IAE.0b013e318156777f 18185143
Chan WM, Lai TY, Lai RY, Tang EW, Liu DT, Lam DS. Safety enhanced photodynamic therapy for chronic central serous chorioretinopathy: one-year results of a prospective study. Retina. 2008;28:85–93.18185143
17. Maruko I Iida T Sugano Y Ojima A Ogasawara M Spaide RF Subfoveal choroidal thickness after treatment of central serous chorioretinopathy Ophthalmology 2010 117 1792 9 10.1016/j.ophtha.2010.01.023 20472289
Maruko I, Iida T, Sugano Y, Ojima A, Ogasawara M, Spaide RF. Subfoveal choroidal thickness after treatment of central serous chorioretinopathy. Ophthalmology. 2010;117:1792–9.20472289
18. Izumi T Koizumi H Maruko I Takahashi Y Sonoda S Sakamoto T Structural analyses of choroid after half-dose verteporfin photodynamic therapy for central serous chorioretinopathy Br J Ophthalmol 2017 101 433 7 10.1136/bjophthalmol-2016-308921 27388248
Izumi T, Koizumi H, Maruko I, Takahashi Y, Sonoda S, Sakamoto T, et al. Structural analyses of choroid after half-dose verteporfin photodynamic therapy for central serous chorioretinopathy. Br J Ophthalmol. 2017;101:433–7.27388248
19. Nishigori N Muraoka Y Ishikura M Kogo T Ueda-Arakawa N Miyata M Extensive reduction in choroidal thickness after photodynamic therapy in eyes with central serous chorioretinopathy Sci Rep 2023 13 10890 10.1038/s41598-023-37802-w 37407690
Nishigori N, Muraoka Y, Ishikura M, Kogo T, Ueda-Arakawa N, Miyata M, et al. Extensive reduction in choroidal thickness after photodynamic therapy in eyes with central serous chorioretinopathy. Sci Rep. 2023;13:10890.37407690
20. Funatsu R Sonoda S Terasaki H Shiihara H Mihara N Horie J Effect of photodynamic therapy on choroid of the medial area from optic disc in patients with central serous chorioretinopathy PLoS ONE 2023 18 e0282057 10.1371/journal.pone.0282057 36809529
Funatsu R, Sonoda S, Terasaki H, Shiihara H, Mihara N, Horie J, et al. Effect of photodynamic therapy on choroid of the medial area from optic disc in patients with central serous chorioretinopathy. PLoS ONE. 2023;18:e0282057.36809529
21. Terao N Koizumi H Kojima K Kusada N Nagata K Yamagishi T Short axial length and hyperopic refractive error are risk factors of central serous chorioretinopathy Br J Ophthalmol 2020 104 1260 5 31780441
Terao N, Koizumi H, Kojima K, Kusada N, Nagata K, Yamagishi T, et al. Short axial length and hyperopic refractive error are risk factors of central serous chorioretinopathy. Br J Ophthalmol. 2020;104:1260–5.31780441
22. Ohno-Matsui K Akiba M Modegi T Tomita M Ishibashi T Tokoro T Association between shape of sclera and myopic retinochoroidal lesions in patients with pathologic myopia Invest Ophthalmol Vis Sci 2012 53 6046 61 10.1167/iovs.12-10161 22879412
Ohno-Matsui K, Akiba M, Modegi T, Tomita M, Ishibashi T, Tokoro T, et al. Association between shape of sclera and myopic retinochoroidal lesions in patients with pathologic myopia. Invest Ophthalmol Vis Sci. 2012;53:6046–61.22879412
23. Mohamed-Noor J Bochmann F Siddiqui MA Atta HR Leslie T Maharajan P Correlation between corneal and scleral thickness in glaucoma J Glaucoma 2009 18 32 6 10.1097/IJG.0b013e31816b2fd1 19142132
Mohamed-Noor J, Bochmann F, Siddiqui MA, Atta HR, Leslie T, Maharajan P, et al. Correlation between corneal and scleral thickness in glaucoma. J Glaucoma. 2009;18:32–6.19142132
24. Imanaga N Terao N Nakamine S Tamashiro T Wakugawa S Sawaguchi K Scleral thickness in central serous chorioretinopathy Ophthalmol Retina 2021 5 285 91 10.1016/j.oret.2020.07.011 32683110
Imanaga N, Terao N, Nakamine S, Tamashiro T, Wakugawa S, Sawaguchi K, et al. Scleral thickness in central serous chorioretinopathy. Ophthalmol Retina. 2021;5:285–91.32683110
25. Lee YJ Lee YJ Lee JY Lee S A pilot study of scleral thickness in central serous chorioretinopathy using anterior segment optical coherence tomography Sci Rep 2021 11 5872 10.1038/s41598-021-85229-y 33712652
Lee YJ, Lee YJ, Lee JY, Lee S. A pilot study of scleral thickness in central serous chorioretinopathy using anterior segment optical coherence tomography. Sci Rep. 2021;11:5872.33712652
26. Fernandez-Vigo JI Moreno-Morillo FJ Shi H Ly-Yang F Burgos-Blasco B Guemes-Villahoz N Assessment of the anterior scleral thickness in central serous chorioretinopathy patients by optical coherence tomography Jpn J Ophthalmol 2021 65 769 76 10.1007/s10384-021-00870-4 34491476
Fernandez-Vigo JI, Moreno-Morillo FJ, Shi H, Ly-Yang F, Burgos-Blasco B, Guemes-Villahoz N, et al. Assessment of the anterior scleral thickness in central serous chorioretinopathy patients by optical coherence tomography. Jpn J Ophthalmol. 2021;65:769–76.34491476
27. Aoki S Asaoka R Azuma K Kitamoto K Ueda K Inoue T Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy Graefes Arch Clin Exp Ophthalmol 2024 262 1795 803 10.1007/s00417-024-06378-0 38285248
Aoki S, Asaoka R, Azuma K, Kitamoto K, Ueda K, Inoue T, et al. Biomechanical properties measured with dynamic Scheimpflug analyzer in central serous chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 2024;262:1795–803.38285248
28. Spaide RF Fisher YL Ngo WK Barbazetto I Regional scleral thickness as a risk factor for central serous chorioretinopathy Retina 2022 42 1231 7 10.1097/IAE.0000000000003485 35344531
Spaide RF, Fisher YL, Ngo WK, Barbazetto I. Regional scleral thickness as a risk factor for central serous chorioretinopathy. Retina. 2022;42:1231–7.35344531
29. Spaide RF Cheung CMG Matsumoto H Kishi S Boon CJF van Dijk EHC Venous overload choroidopathy: a hypothetical framework for central serous chorioretinopathy and allied disorders Prog Retin Eye Res 2022 86 100973 10.1016/j.preteyeres.2021.100973 34029721
Spaide RF, Cheung CMG, Matsumoto H, Kishi S, Boon CJF, van Dijk EHC, et al. Venous overload choroidopathy: a hypothetical framework for central serous chorioretinopathy and allied disorders. Prog Retin Eye Res. 2022;86:100973.34029721
30. Galor A Gregori NZ Margolis TP Which dry eye? The case for precise diagnostic terminology in ophthalmology Ophthalmology 2023 130 239 41 10.1016/j.ophtha.2022.12.001 36610921
Galor A, Gregori NZ, Margolis TP. Which dry eye? The case for precise diagnostic terminology in ophthalmology. Ophthalmology. 2023;130:239–41.36610921
31. Imanaga N Terao N Sonoda S Sawaguchi S Yamauchi Y Sakamoto T Relationship between scleral thickness and choroidal structure in central serous chorioretinopathy Invest Ophthalmol Vis Sci 2023 64 16 10.1167/iovs.64.1.16 36662534
Imanaga N, Terao N, Sonoda S, Sawaguchi S, Yamauchi Y, Sakamoto T, et al. Relationship between scleral thickness and choroidal structure in central serous chorioretinopathy. Invest Ophthalmol Vis Sci. 2023;64:16.36662534
32. Imanaga N Terao N Sawaguchi S Tamashiro T Wakugawa S Yamauchi Y Clinical factors related to loculation of fluid in central serous chorioretinopathy Am J Ophthalmol 2022 235 197 203 10.1016/j.ajo.2021.09.009 34547278
Imanaga N, Terao N, Sawaguchi S, Tamashiro T, Wakugawa S, Yamauchi Y, et al. Clinical factors related to loculation of fluid in central serous chorioretinopathy. Am J Ophthalmol. 2022;235:197–203.34547278
33. Terao N Imanaga N Wakugawa S Sawaguchi S Tamashiro T Yamauchi Y Ciliochoroidal effusion in central serous chorioretinopathy Retina 2022 42 730 7 10.1097/IAE.0000000000003376 34907128
Terao N, Imanaga N, Wakugawa S, Sawaguchi S, Tamashiro T, Yamauchi Y, et al. Ciliochoroidal effusion in central serous chorioretinopathy. Retina. 2022;42:730–7.34907128
34. Spaide RF Ryan EH Jr Loculation of fluid in the posterior choroid in eyes with central serous chorioretinopathy Am J Ophthalmol 2015 160 1211 6 10.1016/j.ajo.2015.08.018 26299534
Spaide RF, Ryan EH Jr. Loculation of fluid in the posterior choroid in eyes with central serous chorioretinopathy. Am J Ophthalmol. 2015;160:1211–6.26299534
35. Uyama M Takahashi K Kozaki J Tagami N Takada Y Ohkuma H Uveal effusion syndrome: clinical features, surgical treatment, histologic examination of the sclera, and pathophysiology Ophthalmology 2000 107 441 9 10.1016/S0161-6420(99)00141-4 10711879
Uyama M, Takahashi K, Kozaki J, Tagami N, Takada Y, Ohkuma H, et al. Uveal effusion syndrome: clinical features, surgical treatment, histologic examination of the sclera, and pathophysiology. Ophthalmology. 2000;107:441–9.10711879
36. Manayath GJ Arora S Parikh H Shah PK Tiwari S Narendran V Is myopia a protective factor against central serous chorioretinopathy? Int J Ophthalmol 2016 9 266 70 26949648
Manayath GJ, Arora S, Parikh H, Shah PK, Tiwari S, Narendran V. Is myopia a protective factor against central serous chorioretinopathy? Int J Ophthalmol. 2016;9:266–70.26949648
37. Iida T Spaide RF Haas A Yannuzzi LA Jampol LM Lesser RL Leopard-spot pattern of yellowish subretinal deposits in central serous chorioretinopathy Arch Ophthalmol 2002 120 37 42 10.1001/archopht.120.1.37 11786055
Iida T, Spaide RF, Haas A, Yannuzzi LA, Jampol LM, Lesser RL. Leopard-spot pattern of yellowish subretinal deposits in central serous chorioretinopathy. Arch Ophthalmol. 2002;120:37–42.11786055
38. Boulanger E Bonnin S Delahaye-Mazza C Tadayoni R Gaudric A Central serous chorioretinopathy mimicking idiopathic uveal effusion syndrome Retin Cases Brief Rep 2023 17 288 93 10.1097/ICB.0000000000001170 34081041
Boulanger E, Bonnin S, Delahaye-Mazza C, Tadayoni R, Gaudric A. Central serous chorioretinopathy mimicking idiopathic uveal effusion syndrome. Retin Cases Brief Rep. 2023;17:288–93.34081041
39. Onoe H Shimada H Kawamura A Hirosawa H Tanaka K Mori R Bilateral pachychoroid disease with type 3 uveal effusion syndrome in one eye and central serous chorioretinopathy in contralateral eye: a case report BMC Ophthalmol 2022 22 91 10.1186/s12886-022-02316-y 35197001
Onoe H, Shimada H, Kawamura A, Hirosawa H, Tanaka K, Mori R, et al. Bilateral pachychoroid disease with type 3 uveal effusion syndrome in one eye and central serous chorioretinopathy in contralateral eye: a case report. BMC Ophthalmol. 2022;22:91.35197001
40. Tran T Okada M Goh J Gin T Harper CA Choroidal effusion as a manifestation of central serous chorioretinopathy: a case report Am J Ophthalmol Case Rep 2022 25 101311 10.1016/j.ajoc.2022.101311 35146193
Tran T, Okada M, Goh J, Gin T, Harper CA. Choroidal effusion as a manifestation of central serous chorioretinopathy: a case report. Am J Ophthalmol Case Rep. 2022;25:101311.35146193
41. Venkatesh P Chawla R Tripathy K Singh HI Bypareddy R Scleral resection in chronic central serous chorioretinopathy complicated by exudative retinal detachment Eye Vis 2016 3 23 10.1186/s40662-016-0055-5
Venkatesh P, Chawla R, Tripathy K, Singh HI, Bypareddy R. Scleral resection in chronic central serous chorioretinopathy complicated by exudative retinal detachment. Eye Vis. 2016;3:23.
42. Maggio E Mete M Maraone G Arena F Pertile G Scleral thinning surgery for bullous retinal detachment with retinal pigment epithelial tear in central serous chorioretinopathy: a case report BMC Ophthalmol 2020 20 133 10.1186/s12886-020-01409-w 32252699
Maggio E, Mete M, Maraone G, Arena F, Pertile G. Scleral thinning surgery for bullous retinal detachment with retinal pigment epithelial tear in central serous chorioretinopathy: a case report. BMC Ophthalmol. 2020;20:133.32252699
43. Chhablani J Cohen FB Central Serous Chorioretinopathy International Group Multimodal imaging-based central serous chorioretinopathy classification Ophthalmol Retina 2020 4 1043 6 10.1016/j.oret.2020.07.026 33131671
Chhablani J, Cohen FB, Central Serous Chorioretinopathy International Group. Multimodal imaging-based central serous chorioretinopathy classification. Ophthalmol Retina. 2020;4:1043–6.33131671
44. Imanaga N Terao N Wakugawa S Miyara Y Sawaguchi S Oshiro A Scleral thickness in simple versus complex central serous chorioretinopathy Am J Ophthalmol 2024 261 103 11 10.1016/j.ajo.2024.01.025 38281567
Imanaga N, Terao N, Wakugawa S, Miyara Y, Sawaguchi S, Oshiro A, et al. Scleral thickness in simple versus complex central serous chorioretinopathy. Am J Ophthalmol. 2024;261:103–11.38281567
45. Sawaguchi S Terao N Imanaga N Wakugawa S Tamashiro T Yamauchi Y Scleral thickness in steroid-induced central serous chorioretinopathy Ophthalmol Sci 2022 2 100124 10.1016/j.xops.2022.100124 36249703
Sawaguchi S, Terao N, Imanaga N, Wakugawa S, Tamashiro T, Yamauchi Y, et al. Scleral thickness in steroid-induced central serous chorioretinopathy. Ophthalmol Sci. 2022;2:100124.36249703
46. Terao N Imanaga N Wakugawa S Sawaguchi S Tamashiro T Yamauchi Y Short axial length is related to asymmetric vortex veins in central serous chorioretinopathy Ophthalmol Sci 2021 1 100071 10.1016/j.xops.2021.100071 36246946
Terao N, Imanaga N, Wakugawa S, Sawaguchi S, Tamashiro T, Yamauchi Y, et al. Short axial length is related to asymmetric vortex veins in central serous chorioretinopathy. Ophthalmol Sci. 2021;1:100071.36246946
47. Bacci T Oh DJ Singer M Sadda S Freund KB Ultra-widefield indocyanine green angiography reveals patterns of choroidal venous insufficiency influencing pachychoroid disease Invest Ophthalmol Vis Sci 2022 63 17 10.1167/iovs.63.1.17 35019945
Bacci T, Oh DJ, Singer M, Sadda S, Freund KB. Ultra-widefield indocyanine green angiography reveals patterns of choroidal venous insufficiency influencing pachychoroid disease. Invest Ophthalmol Vis Sci. 2022;63:17.35019945
48. Mori K Gehlbach PL Yoneya S Shimizu K Asymmetry of choroidal venous vascular patterns in the human eye Ophthalmology 2004 111 507 12 10.1016/j.ophtha.2003.06.009 15019327
Mori K, Gehlbach PL, Yoneya S, Shimizu K. Asymmetry of choroidal venous vascular patterns in the human eye. Ophthalmology. 2004;111:507–12.15019327
49. Aichi T Terao N Imanaga N Sawaguchi S Wakugawa S Miyara Y Scleral thickness in the fellow eyes of patients with unilateral central serous chorioretinopathy Retina 2023 43 1573 8 10.1097/IAE.0000000000003850 37262427
Aichi T, Terao N, Imanaga N, Sawaguchi S, Wakugawa S, Miyara Y, et al. Scleral thickness in the fellow eyes of patients with unilateral central serous chorioretinopathy. Retina. 2023;43:1573–8.37262427
50. Hirooka K Saito M Yamashita Y Hashimoto Y Terao N Koizumi H Imbalanced choroidal circulation in eyes with asymmetric dilated vortex vein Jpn J Ophthalmol 2022 66 14 8 10.1007/s10384-021-00889-7 34860297
Hirooka K, Saito M, Yamashita Y, Hashimoto Y, Terao N, Koizumi H, et al. Imbalanced choroidal circulation in eyes with asymmetric dilated vortex vein. Jpn J Ophthalmol. 2022;66:14–8.34860297
51. Sirks MJ van Dijk EHC Rosenberg N Hollak CEM Aslanis S Cheung CMG Clinical impact of the worldwide shortage of verteporfin (Visudyne®on ophthalmic care Acta Ophthalmol 2022 100 e1522 32 10.1111/aos.15148 35388619
Sirks MJ, van Dijk EHC, Rosenberg N, Hollak CEM, Aslanis S, Cheung CMG, et al. Clinical impact of the worldwide shortage of verteporfin (Visudyne®) on ophthalmic care. Acta Ophthalmol. 2022;100:e1522–32.35388619
52. Sato Y Ueda-Arakawa N Takahashi A Miyara Y Hara C Kitajima Y Clinical characteristics and progression of geographic atrophy in a Japanese population Ophthalmol Retina 2023 7 901 9 10.1016/j.oret.2023.06.004 37302656
Sato Y, Ueda-Arakawa N, Takahashi A, Miyara Y, Hara C, Kitajima Y, et al. Clinical characteristics and progression of geographic atrophy in a Japanese population. Ophthalmol Retina. 2023;7:901–9.37302656
53. Hosoda Y Miyake M Yamashiro K Ooto S Takahashi A Oishi A Deep phenotype unsupervised machine learning revealed the significance of pachychoroid features in etiology and visual prognosis of age-related macular degeneration Sci Rep 2020 10 18423 10.1038/s41598-020-75451-5 33116208
Hosoda Y, Miyake M, Yamashiro K, Ooto S, Takahashi A, Oishi A, et al. Deep phenotype unsupervised machine learning revealed the significance of pachychoroid features in etiology and visual prognosis of age-related macular degeneration. Sci Rep. 2020;10:18423.33116208
